Synthesis of cyclobutanones by the photolytic reaction of chromium

J. Am. Chem. Soc. 1990, 112,4364-4374

4364

before it was partitioned between EtOAc (IO mL) and brine (5 mL). The layers were separated, and the organics were washed with brine (5 mL), and the combined aqueous layers were extracted with EtOAc (2 X 5 mL). The organics were dried (MgSO,) and filtered, and the solvents were removed to give 0.7 mg of the deacylated amide as a slightly yellow oil that was used in the next step without further purification: oil; analytical TLC (silica gel F254), 1:l EtOAc/hexane, R, = 0.30; 270MHzNMR(CDCI3)67.39-7.I2(5H,m),6.41 (1 H , d d d , J = 1 . 8 , 3 . 9 , 16.0Hz),5.63(1 H , d d , J = 5 . 6 , 1 5 . 4 H z ) , 5 . 5 9 ( 1 H , d , J = 2 . 3 H z ) , 5.46 ( 1 H, s), 5.34 (1 H, d, J = 5.3 Hz), 5.17 (1 H, ddd, J = 7.1, 7.7, 15.4 Hz), 5.15 ( I H, s), 5.05 (1 H,ddd,J= 4.4,6.8, 16.0 Hz), 4.99 (1 H, s), 4.77-4.74 ( I H, m), 3.90 (1 H, d, J = 3.29 Hz), 3.29-3.19 (1 H, m), 2.92-2.73 (3 H, m), 2.61 (1 H, dd, J = 9.8, 13.3 Hz), 2.46-2.43 (1 H, m), 2.35-2.,26 ( I H, m), 2.23 (3 H, s), 2.13-1.96 (2 H, m), 1.15 (3 H,d,J=7.1 H z ) , l . O 2 ( 3 H , d , J = 7 . 1 Hz),O.81(9H,s),-O.O3(6H, S).

The amide (0.7 mg) was dissolved in CH,CN (0.1 mL) and cooled to 0 OC then 48% (aqueous) H F was added ( I pL, 24 pmol) and the reaction was stirred for 100 min at 0 OC and then partitioned between EtOAc (5 mL) and brine (5 mL). The organics were washed with brine (5 mL), the combined aqueous layers were bakc-extracted with EtOAc (2 X 5 mL), and then the organic portion was dried (MgSO,) and filtered, and the solvents were evaporated. The residue was purified by

ATLC (5 cm X IO cm, 3:l EtOAc/hexane) to give dl-C18-desmethylcytochalasin D (32),0.5 mg (ca. 70% for two steps): white crystals from acetone/hexane; mp 232-236 OC dec; analytical TLC (silica gel F254), 3:l EtOAc/hexane, Rf = 0.41; MS exact mass calcd for C29H3SN06 493.2464, found 493.2472, error = 1.6 ppm; IR (neat, cm-I) N H and O H 3340, C=O 1740, C 4 1690, C 4 1685; 2 7 0 - M H ~NMR (CDCI,) d 7.35-7.1 1 (5 H, m), 6.50 (1 H, dd, J = 1.8, 16.0 Hz), 5.77 (1 H, dd, J = 9.2, 15.4 Hz), 5.55 (1 H, dd, J = 2.4, 2.7 Hz), 5.51 ( I H, d, J = 0.9 Hz), 5.44 ( I H, s), 5.37 (1 H, ddd, J = 6.8, 7.4, 15.4 Hz), 5.10 ( I H, ddd, J = 2.7, 5.0, 16.0 Hz), 4.78-4.75 (1 H, m), 3.82 (1 H, dd, J = I.5,10.9Hz),3.35-3.25(2H,m),2.94(1 H,dd,J=3.88,13.3Hz), 2.80 (1 H, dd, J = 10.0, 11.0 Hz), 2.80-2.73 (1 H, m), 2.56 (1 H, dd, J = 9.8, 13.3 Hz), 2.38-2.28 (2 H, m), 2.21 (3 H, s), 2.19-2.05 (3 H,

m),1.97(lH,s),1.15(3H,d,J=7.1Hz),l.ll(3H,d,J=6.8Hz).

Acknowledgment. This work was supported by the National Institutes of Health (Grant No. CA-17918). Supplementary Material Available: Table of mass spectral fragmentation patterns for 32,CD, and ZE and details of the route to C,6-epi-zygosporin E (5 pages). Ordering information is available on any current masthead page.

Synthesis of Cyclobutanones by the Photolytic Reaction of Chromium Carbene Complexes with Olefins: Inter- and Intramolecular Reactions Bjorn C. Soderberg, Louis S. Hegedus,* and Miguel A. Sierra Contribution from the Department of Chemistry, Colorado State University, Fort Collins, Colorado 80523. Received October 9,I989

Abstract: Cyclobutanones were synthesized in good yield and with a high degree of stereo- and regioselectivityby the photolytic reaction between a variety of chromium alkoxycarbene complexes and olefins. Bicyclic cyclobutanones were synthesized in good yield and with a high degree of stereo- and regioselectivity by the photolysis of chromium alkoxycarbenes having remote double bonds in the alkoxy group.

Photolysis reactions of heteroatom-stabilized (Fischer) chromium carbene complexes are becoming increasingly useful for the synthesis of novel organic compounds under exceptionally mild conditions. Thus photolysis, using visible light and a Pyrex reaction vessel, in solvents ranging from hexane through acetonitrile, of methoxycarbenes' and aminocarbenes* with imines produced P-lactams in excellent chemical yield. Use of optically active aminocarbene complexes3 resulted in the production of optically active P-lactams in good yield and with high ~tereoselectivity.~ Photolysis of aminocarbene complexes in the presence of alcohols produced a-amino acid e ~ t e r s . During ~ the development of these reactions it became clear that photolysis of chromium carbene complexes produced species that reacted as if they were ketenes, although no evidence for the generation of free ketenes was observed.6 This suggested that other classes of reactions in which ( I ) Hegedus, L. S.; McGuire, M. A.;Schultze, L. M.; Yijun, C.;Anderson, 0. P. J. Am. Chem. SOC.1984, 106, 2680. (2) Borel, C.; Hegedus, L. S.; Krebs, J.; Satoh, Y. J.Am. Chem. Soc. 1987, 109, 1101.

( 3 ) Imwinkelried, R.; Hegedus. L. S. Organometallics 1988, 7, 702. (4) Hegedus, L. S.; Imwinkelried, R.; Alarid-Sargent. M.; Dvorak, D.; Satoh, Y. J . Am. Chem. Soc. 1990, 112, 1109. ( 5 ) Hegedus, L. S.; Schwindt, M. A.; DeLombaert, S.; Imwinkelried, R. J . Am. Chem. Soc. 1990, 112, 2264.

ketenes engaged should be examined. Stereospecific [2 21 cycloaddition' reactions of ketenes and olefins to produce cyclobutanoned' have been extensively developed, although the use of electron-rich 0- or N-containing ketenes is u n c ~ m m o n . ~In contrast, intramolecular versions of this process

+

(6) (a) Hegedus, L. S.; deWeck, G.;DAndrea, S. J . Am. Chem. Soc. 1988, 110, 2122. (b) Cyclobutanones have also been produced by intramolecular trapping of chromium-vinyl ketene complexes, produced by the thermal reaction of chromium-arbene complexes with enynes, see: Wulff, W. D.; Kaisler, R. W . Organometallics 1985,4, 1461. Korkowski, P. F.; Hoye, T. R.; Rydberg, D. B. J . Am. Chem. Soc. 1988, 110, 2676. (c) Reaction of (phenyl)(methoxy)carbenMhromium complexes with enamides under I50 atm of CO pressure also produced cyclobutanones: Dorrer, B.; Fischer, E. 0. Chem. Ber. 1974, 107, 2683. (d) Treatment of (ethoxy)(triphenylsilyl)tungsten carbenes under 50 atm of CO produced the free ketene which was isolated and/or allowed to react with enol ethers to form cyclobutanones: Schubert, U.;Uron, J.; Hornig, H. J . Organomet. Chem. 1988, 355, 243. Uron, J.; Schubert, U. Ibid. 1989, 373, 203. (7) (a) Ghosez, L.; ODonnell, J. M. Pericyclic Reactions; Marchand, A. P., Lehr, R. E., Eds.; Academic Press: New York, 1977; Vol. 11, pp 79-140. (b) Brady, W. T. Teirahedron 1981, 37, 2949. (c) Brady, W. T. The Chemistry of Ketenes, Allenes, and Related Compounds; Patai, S., Ed.; Interscience Publications: New York, 1980; pp 278-308. (8) Bellus, D.; Ernst, 8. Angew. Chem., Int. Ed. Engl. 1988, 27, 797. (9) (a) Reichen, W. Chem. Rev. 1978,78,568. (b) Brady, W. T.; Gu, Y. Q.J . Org. Chem. 1989, 54, 2834.

0002-7863/90/ 15 12-4364$02.50/0 0 1990 American Chemical Society

J . Am. Chem. SOC..Vol. 112, No. 11, 1990 4365

Reaction of Chromium Carbene Complexes with Olefins Table 1. Conversion of Monoolefins to Cyclobutanonesby Reaction with Complex 1

olefin 2

cyclobutanone 3

yield, %"

isomerb ratio

44

1O:l

31

1O:l

51

5:1

13

5:1

77

single isomer

@

2b

0

3b

/-7 2c

+

3d (8%)

+

3c(2%)

0 3c

& 2d

M

y

0

3d

d 2e

3e (45%)

T 21

3e' (3%)

3f

Reported yields are for isolated, purified materials. Determined b) 'H NYR spectroscopy, and ratio confirmed by gas chromatography. The minor isomer had the substituent syn to the methoxy group. Isomers were not separated. have been extensively investigated, primarily by SniderIo and Brady. The requisite ketene precursors, (a1kenyloxy)acetic acids, were available from the unsaturated alcohol and bromoacetic acid, and the intramolecular cycloaddition, in general, proceeded more efficiently than did the intermolecular version. Photolysis of readily available (alkoxy)- or (alkeny1oxy)carbene chromium complexes should provide ready access to these classes of electron-rich ketenes. Indeed. preliminary studies in these laboratories have shown photolysis of chromium (a1koxy)carbenes in the presence of a range of simple olefins produced cyclobutanones in excellent yield (eq Herein the full details of the synthesis of cyclobutanones by the inter- and intramolecular photoreactions of chromium (a1koxy)carbene complexes with olefins are reported.

3

Results and Discussion (a) Intermolecular Reactions. Because of the paucity of data concerning the use of alkoxyketenes in the synthesis of cyclobutanones, a wide range of olefinic substrates was examined for reactivity. The results of the reaction of (methoxy)(methyl)carbene 1 with simple, unfunctionalized monoolefins are summarized in Table 1. Several features warrant comment. Although the yields of isolated, purified products were only modest, crude yields were high, and the lower isolated yields are, in part, due to the volatility of the products. The reaction was quite stereoselective, resulting in the syn disposition of large groups in the major isomer, as is usually observed in ketene-olefin cycl~additions.~~*J~ (The (IO) Snider, B. B. Chem. Reo. 1988.88.793 and references cited therein. ( I I ) Sierra, M. A.; Hegedus, L. S.J . Am. Chem. Soc. 1989, I l l , 2335. (12) DoMinh, T.; S t r a w , 0. P. J . Am. Chem. Soc. 1970, 92, 1766.

isomers could not be separated.) With cis and trans-2-butene (2c and 2d), the stereochemistry of the olefin was maintained. truns-2-Butene was much less efficient in this reaction than was the cis isomer. In both cases, small amounts of the opposite olefin stereochemistry were observed after chromatographic purification and was attributed to epimerization of the position a to the carbonyl group. The reaction was also regioselective, giving the product resulting from attack of the more nucleophilic olefin carbon on the electrophilic ketene carbonyl carbon. (This regiochemistry was readily confirmed by the presence of a dd in the 6 2.5-3.0 region of the IH N M R spectrum due to the diastereotopic CH2 group a to the carbonyl group.) In addition, geminally disubstituted olefin 2e gave minor amounts of the opposite regioisomer, while 3f gave a single stereo- and regioisomer, but the stereochemistry of the lone methyl group could not be assigned. When run in ether solvent under a modest (90 psi) pressure of carbon monoxide, the reaction was remarkably clean, and Cr(C0)6,which precipitated from solution, could be recovered in 60-70% yield and reused. The expected syn stereochemistry in these products was confirmed by 'H NMR spectroscopy experiments in several cases. For example, the major isomer of 3a had the phenyl group and the methyl group syn, as evidenced by the relatively high field (6 1.01) absorption of the methyl group due to the shielding by the syn phenyl group. The methoxy signal was at 6 3.50. In contrast the minor isomer had 6 OMe at 3.08, indicating a syn relation to the phenyl group, and 6 Me at 1.54.13 Cyclic conjugated dienes also underwent this reaction in good yield (eq 2 and 3). The major stereoisomer in all cases had the two large groups (R and the ring) syn and the alkoxy group exo, as evidenced by the upfield chemical shift of the R group in the major isomer relative to the minor isomer (e.g., 6 1.07 vs 1.41 for 5; 6 1.17 vs 1.52 for 7a; 6 1.13 vs 1.50 for 7e; 6 1.30 vs 1.54 for 7g).'4 hv

I

ti

Me Ma.*?\

5: 67% (1O:l) R

6s: R = Me. R' = Me = 1

b : R = d R'=Me c: R = nBu. R' = Me d: R = Ph. R'= Me e: R = Me, R' = El 1: R = nBu. R' = Et g: R = Me, R' = CH2Ph h:R=Me,R'=TMS i: R = P h C H E C H , R' = Me

"

H

H

7a:52% (1 4:1) b: 48% (2O:l) C: 46% (13:l) d: 75% (20:l) e: 85% (1O:l) f: 96% (14:l) 9: 70% (9:1) h: 37% (5:l)

The reaction was not restricted to the parent carbene complex 1, but rather tolerated a variety of alkyl and alkoxy groups (eq

3). The yields with these carbene complexes were high, and again, the same stereo- and regioselectivity as with simple cases was observed. The ease of synthesis of structurally varied alkoxycarbene complexes makes this an attractive alternative to conventional ketene m e t h o d ~ l o g yfor ~ ~which the requisite a-alkoxy acid chlorides may be difficult to prepare. However, a,@-unsaturated carbene complexes (69 failed to form cyclobutanones when photolyzed with a variety of olefins. Instead, photodecomposition of the carbene to a myriad of unidentified products occurred. ( I 3) In related 8-azetidinones, methoxy groups syn to phenyl groups appeared at -6 3.0, while those anti appeared at 6 3.6. See also: Bose, A. K.; Lal, B.; Manko, M. S. Tetrahedron Lett. 1974, 2633. (14) (a) Rey, M.; Roberts, S. Dieffenbacher.A.; Dreiding, A. S. Helo. Chim. Acta 1970.53,417. (b) Brady, W. T.; Roe, R., Jr. J . Am. Chem. Soc. 1970,92,4618. (c) Brady, W. T.; Roe, R., Jr. J . Am. Chem. SOC.1971, 93, 1662.

Soderberg et al.

4366 J . Am. Chem. Soc.. Vol. I 12, No. I I I990 ~

Table 11. Conversion of Electron-Rich Olefins to Cyclobutanones by Reaction with Complex 1 isomerbSC olefin 9 cyclobutanone 10 yield, 410" ratio &X

M+f

P

0

9a: X = OEt 9b: X = OAC 9 ~X: = NHAC

9

9d:X=N 0

loa: X = OEt 1Ob: X = OAC 1OC: X = NHAc 10d: X = N

87 78

6 :1 20: 1 8: 1 7: 1

80

I1:I

19

96

9e 1Oe

1:l

10f (16%)

+

.*,hOk 0

1Of' (3%) single isomer

" Reported yields are for isolated, purified material. Determined by 'H NMR spectroscopy. The minor isomer had the olefin substituent syn to the methoxy group. Clsomers were not separated. The behavior of oxacyclopentylidenecomplex 6j was particularly interesting (eq 4). Under the standard reaction conditions (hv, Et,O, 90 psi CO) cyclobutanone 7j was formed as the major product, along with a small amount of cyclopropane 8. In the absence of CO, the cyclopropane was the major product. Thermal reactions of alkoxycarbene complexes with olefins normally produce cyclopropanes.I5 However heating carbene 6j with cyclohexadiene to 95 OC in the presence and absence of CO (sealed tube) for prolonged periods resulted in no reaction at all. Instead

7j: 55% (1511)

8: 11%

8: 27%

95 'c €120

noreaction

carbene 6j was recovered in excellent yield. Since a vacant coordination site is required for cyclopropanation of electron deficient olefins, thermal, sealed-tube reactions of complex 6j did not occur, since generation of a coordination site by CO loss was suppressed. I n contrast the results shown in eq 4 imply that under photochemical conditions concentration of unsaturated complex sufficient to form cyclopropanes competitively are generated, even under modest CO pressures. Complex 6j is unusual among alkoxycarbene complexes in that the 53CrNMR signal appears well upfield from those of noncyclic alkoxycarbenes (6 123 vs 170-300), a fact attributed to an increase in shielding of the metal by the enforced efficient A overlap of the lone pair of electrons on oxygen with the sp2 carbene carbon.I6 This results in an increase in (IS) (a) D6tz, K. H.; Fischer, E. 0. Chem. Ber. 1972, 105. 1356. (b) Wienand, A.; Reissig, H.-U. Tezrohedron Lett. 1988, 29, 2315. (c) Buckert, M.;Reissig, H.-U. Tetrahedron Lert. 1988, 29. 2319. (d) m t z , K. H. Angew Chem., Int. Ed. Engl. 1984, 23, 587 and references therein. (16)Hafner, A.; Hegedus, L.S.;deWeck, G.; Hawkins, B.: DBtz, K. H. J. Am. Chem. SOC.1988,110, 8413.

stability of the carbene complex and may well make CO insertion more difficult. Electron-rich olefins also underwent this cycloaddition reaction efficiently (Table 11). Enol ethers and enamides formed cyclobutanones in excellent isolated yield and with the same stereo and regioselectivity observed with simple olefins. In contrast, enol acetates (9b, f) underwent reaction in only low yield, with concommitant formation of many byproducts. Allyl acetate (Table I) had similar problems. As was the case with simple olefins, gem disubstitution (9f)resulted in the production of two regioisomers (lOf, 1Of') with the major regiosomer 1Of being a 1:l mixture of stereoisomers and the minor regioisomer 1Of' being a single stereoisomer. In contrast to most ketene-olefin reactions large excesses of olefin were not required for good conversion, since ketene-ketene reactions are not observed in photolyses of chromium carbene complexes. Thus, with 9e as substrate, the yield was 80% when 5 equiv of olefin is used and a respectable 65% when only 1 equiv is used. In addition, both yields and isomer distributions were insensitive to solvent and concentration. The methyl group of the major isomer again appeared upfield from that of the minor isomer (loa, 6 1.35 vs 1 .57; IOc, 6 1.27 vs 1S4; lOe, 6 1.20 vs 1.56), indicative of the syn disposition of this methyl group and the heteroatom substituent from the olefinic partner in the reaction.'& The assigned stereochemistry was confirmed by NOE measurements on 10a and 1Oc. Thus, the irradiation of the C-2 Me0 signal in 1Oa resulted in strong NOE enhancement of the adjacent C-3 CH signal, whereas irradiation of the C-2 Me signal resulted in no enhancement of this same signal, indicating the syn relation of the M e 0 group and the C-3 C H group and confirming the assigned stereochemistry of loa. The same NOE measurements were carried out on 1Oc with the same results. A direct comparison of the chromium carbene route to cyclobutanones with the conventional acid chloride/tertiary amine methodology is instructive. The [2 21 cycloaddition of (menthy1oxy)methylketeneto ethyl propenyl ether was recently reported (eq 5)." The same reaction was carried out by using the methodology developed herein (eq 6). The processes gave similar results in many respects. The overall chemical yield of its carbene route was substantially higher, primarily because the requisite carbene 12 was synthesized in much better yield than the corresponding acid halide. The yields for the cycloaddition step were comparable, with the carbene route having a slight edge. The diastereoselectivity was identical, as was the intrinsic (initial) cis/trans isomer ratio about the enol ether derived fragment. (The cis enol reacts faster than the trans isomer, accounting for the preponderance of Ilb.) After 1 h, the reaction mixture in eq 5 was reported to consist of a 1:9 mixture of 1 la and 1 l b (7% conversion not reported). Base-catalyzed epimerization of l l b to l l a over the 20 h course of the reaction accounts for the final preponderance of the more stable trans-lla. In contrast, no epimerization was noted in the carbene route (eq 6) since the conditions were milder (25 OC, neutral). /-(-)-menthol + CO,Et NaH KOH yC02H

+

__.t

Br (4:l ckjrans)

DMF

MeOH

M & O q

+

OMen (31"10)

M ; n O d

EIO-

(5)

OMen

ElrN ~ B ~ O reflux H.

EIO"'

(77%)

M h

,118(1:3)

EtO"

"5,

11b(l:3)

,

after 1 h; %axversion not reported) overall 16% from I - (-) - menthol

65% (4:l) (1.9

A number of olefins failed to convert cleanly to cyclobutanones when irradiated with complex 1. Acrolein dimethyl acetal, 1chlorocyclohexene, 2-methyl-l-bromopropene,furan, 2,3-dimethyl-2-butene, phenylacetylene, diphenylacetylene, ethoxy( I 7) Frlter, G.; Miiller, U.;Giinther, W. Helu. Chem. Acto 1986.69, 1858.

J. Am. Chem. SOC.,Vol. 112, No. 11, 1990 4367

Reaction of Chromium Carbene Complexes with Olefins

Table 111. Photolytic Synthesis of Cyclobutanones from

ONMe4 1. CH3COEr

COW^=(

CH3

(Alkeny1oxy)carbenes

c 2. I - (-) .menthol

-

alcohol

( 2 1 dsjrans)

OMen

(CO),Cr3(

hv 23h,WpiCO

CH3 12 (63YO)

11s

+

product 15 (yield, "/ob) C

Ilb

(1:3)

carbene complex 14 (yield, %O)

(6)

(13)

L

T

74% (1:9) (overall 47% from I - (-)

14. (56)

- menthol)

acetylene, ketene diethyl acetal, ethylene, acrylonitrile, methyl acrylate, and 3-methyl- 1,2-butadiene all were consumed in the reaction, but produced complex mixtures of unidentified products. However, given these limitations, the above procedure provides an efficient and convenient approach to a wide variety of alkoxycyclobutanones. The conditions are exceptionally mild and should tolerate a wide range of functional groups. The precursor carbene complexes are readily prepared and can be structurally diverse. The Cr(C0)6 precursor to the carbene complexes is recovered and can be reused. This procedure should be competitive with or superior to standard methodology involving generation of alkoxyketenes by base-assisted elimination of HCl from cyalkoxy acid chloride^.'^*^* (b) Intramolecular Reactions. The requisite (alkeny1oxy)carbene complexes 14 were readily prepared by exchange of the unsaturated alcohol with (acy1oxy)carbene complexes, generated by the reaction of acylate complex 13 with acetyl bromide or pivaloyl chloride (eq 7).16 In contrast to simple alkoxycarbene complexes, those containing remote olefinic groups were relatively unstable, decomposing over the course of a few hours at room temperature and a few weeks at -20 O C . As a consequence, the IH NMR spectra were often broad and ill-resolved (although the I3Cspectra were excellent), their mass spectra, both electron impact and chemical ionization, showed only a fragment corresponding to the parent ion less Cr(CO)5,and acceptable elemental analyses could not be obtained. They were best prepared and used without excessive handling. This instability is almost certainly due to a competing, facile intramolecular cyclopropanation reaction. Indeed, phenylcarbene 16 proved to be unstable above -20 O C even under 90 psi of CO and could not be isolated, converting instead to the cyclopropane 17 in excellent yield (eq 8). Intermolecular cyclopropanation usually requires extended reaction times at elevated temperature and the use of activated olefins as substrate^.'^ However, decomposition of carbenes related to 16 to cyclopropanes has been previously noted.I9

-OH

-0

(w),Cr* M.

14b (75)

Jb Me

15b (88)

14C (55)

15e (62)

'+bo'

Me

u- fie 1E.d (47)

15e'(22)

-

OH

-0 (COhCr=( M.

14h (61)

4

0

15h (73)

0

- 0"

+ 1.

)r!-

&x * (CO)&r=I

(cO)5cr=i 'Me

2.

)n\OH

13

\ lSV(97. - 2 1 ) C

Me 14

hv

I

I

M.

141(56)

C

1"

1. MeLi 2. Me,NBr

psi co Me

14k (56) C

M.

15

141 (63)

Notwithstanding this instability, most carbene complexes studied were sufficiently stable to be isolated, purified, and sub14m (74)

(18) (a) Aben, R . W.; Scheeren, H. W. J . Chem. Soc., Perkin Trans. / 1979, 3132. (b) Bellus, D. J . Org. Chem. 1979, 44. 1208. ( 1 9) (a) Casey, C. P.; Shusterman, A. J. Organomerallics1985,4736 and references therein. (b) Casey, C. P.; Hornung, N. L.; Kosar, W. P. J . Am. Chem. Soc. 1987, 109,4908 and references therein (similar intramolecular cyclopropanations have been observed with tungsten carbene complexes). (c) Alvarez, C.; Parker, A.; Daran, J. C.; Rudler, H.; Rudler, M.; Unobler, C. J . Orgunomct. Chem. 1987. 328, 357 and references therein.

14n (26)

v

;Yields (unoptimized) are of isolated, purified material. bYields are of isolated purified by chromatography or distillation. CComplex mixturc of compounds. From oxidation of unconsumed carbene complex.

Soderberg et al.

4368 J . Am. Chem. SOC,,Vol. 112, No. 1 1 , 1990

jected to photolytic cyclization. Photolysis (visible light through Pyrex) of these complexes in ether solvent under a modest pressure (90 psi) of carbon monoxide produced the bicyclic cyclobutanones 15 and regenerated chromium hexacarbonyl (eq 7). The results of these experiments are summarized in Table 111. These results have many features in common with those observed by using conventional acid chloride/amine ketene generation.I0 (Some differences were also noted, although these may be due to the differences in the structures of the respective ketenes-viz. CH3vs H.) Thus, both types of reactions failed with allyl alcohol derived ketene precursors (e.g. 14a), which would lead to relatively unstable bicyclo[2.2.0] hexanones or bicyclo[2.1.l]he~anones.~~ Instead a complex mixture of products was obtained. In contrast, homoallylic alcohol derived systems (e& 14b-g) were generally successful with both types of reactions, although differences in the effects of olefin substitution on the two classes of reactions were substantial. With monosubstituted alkenes, the conventional route was very inefficient (-20% yield) whereas the carbene route (14b 15b) gave an excellent yield of the same type of product. Both systems gave bicyclo[3.2.0]hexanones when the internal carbon of the alkene was more highly substituted (14b-f) and bicyclo[3.1 .I]heptanones when the terminal carbon of the olefin was more highly substituted (14g), and the yields were comparable. With the carbene system, trans disubstituted ketene precursor 14d gave bicyclo[3.2.0] hexanone 15d in fair yield, while the cis isomer 14e gave a mixture of bicyclo[3.2.0]hexanone 15e and bicyclo[3.1 .I]heptanone 15e' in fair yield. In contrast, with the conventional system the cis disubstituted acid chloride did not react at (No data was reported for the trans isomer.) (Related alkoxyketeniminium salts were more reactive, the cis compounds giving the same types of products as observed with carbene 14e, while the corresponding trans isomer underwent acylation of the olefin rather than cyclobutanone formation.%) With the one carbon longer homologue (e.g. 14h), both systems produced bicyclo[4.2.0]octanones in good yield. Carbene complex 14i efficiently produced tricyclic products 15i and 15i' as an inseparable 2:l mixture of isomers. The structure assignments for 15b-i and for 20 and 21 were based primarily on IH and 13C N M R data, and closely parallel those described by SniderB for identical or closely related systems. Bicyclo[3.2.0] and -[4.2.0] systems having a CH2 group adjacent to the cyclobutanone carbonyl group (15&f,h,ij and 20 and 21) were characterized by a geminal coupling constant for this group of 17-1 9 Hz, much larger than any coupling constant found in the isomeric [3.1.1] or [4.1.1] systems, as well as a "C chemical shift for the carbonyl carbon between 6 210-217. In addition, a strong parent-ketene fragment, only possible from these ring systems, was present in the mass spectrum of each of these compounds. I n contrast, bicyclo[3.1.1] systems 15e' and 15g had "C chemical shift for the carbon at 6 207 and 209, respectively, and a single proton (Y to the carbonyl group in the IH NMR spectrum with JVi,of -0, and 5 Hz unique to this ring system. The mass spectrum of these systems showed no fragment due to loss of ketene, since from this connectivity ketene cannot be lost. The IH and I3C NMR spectra of 1%' and 15g very closely corresponded in both chemical shift and coupling with these same systems lacking the bridgehead methyl, previously prepared by Snider.2o There was a similar correspondence in spectra between 15d and 15e and the corresponding 1-desmethyl compound pre-

-

(20) Snider, B. B.; Hui, R. A. H. F. J. Org. Chem. 1985, 50, 5167.

pared by Snider.2o Isomeric 1% and 15e were easily distinguished by the magnitude of Js,6 = 5 Hz for trans-1% and 10.4 Hz for ~ i s - 1 5 e .Thus ~ ~ the structural assignments are secure. A number of (alkeny1oxy)- and (alkyny1oxy)carbene complexes failed to produce cyclobutanones. In the cases of 14j-I, the carbene was completely consumed, but a complex mixture of unidentified products was obtained. In contrast, long-chain carbene 14m and cyclohexenylcarbene 1411were relatively unreactive, and substantial amounts of carbene remained after 24 h of irradiation. Oxidation of the remaining carbene complex produced the esters which were isolated. The intramolecular cycloaddition reactions of phenoxyketenes to olefins to give tricyclic cyclobutanones has also been extensively studied.2' This chemistry is not accessible via related chromium carbene chemistry, since o-allylphenols failed to exchange with o-acetyl carbene complexes (as in eq 1). However, variation in the alkyl group on the carbene was tolerated. Both cyclopropyl complex 18 and benzyl complex 19, efficiently converted to the corresponding cyclobutanones (eq 9).

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The carbene-complex-based synthesis of bicyclic cyclobutanones complements existing methodology. The ease of preparation of a wide variety of differently substituted alkyl carbene complexes coupled with the very mild conditions for the cycloaddition process make this an attractive approach for the synthesis of functionalized or sensitive systems. Finally, the issue of the nature of the reactive intermediates formed upon photolysis of the carbene complex remains. The following observations are germane. Photolysis of chromium carbene complexes in the presence of suitable ketene traps-olefins, alcohols, amines, imines-results in the production of the same products with the same chemo-, regio-, and stereoselectivity one would expect from the corresponding reaction of the free ketene were it available. However, free ketene cannot be detected in solution when these same carbene complexes are photolyzed in the absence of a ketene trap, nor are ketene-derived products, such as dimers, produced. Indeed, the (methyl)(methoxy)carbene complex 1 can be recovered in excellent yield after days of photolysis in the absence of a ketene trap, although photolysis in the presence of a ketene trap, results in complete consumption of the carbene complex in a matter of hours, and good yields of product are obtained. Thus, any ketene formed by photolysis must remain in close association with the chromium fragment, and must be able to revert to the original carbene complex in the absence of reactive substrates. This behavior stands in marked contrast to the behavior of less stable carbenes, which thermally and/or under a pressure of carbon monoxide liberate free ketenes which can be spectroscopically detected and in many cases, isolated [e& (C0)5Cr=C(Ph)2,23 (CO)5W=C(OEt)(SiPh3)6]. Whatever the precise details of this process, photolysis of chromium alkoxycarbene complexes in the presence of olefins results in the efficient synthesis of cyclobutanones.

Experimental Section General Procedure. Melting points were taken on a Mel-Temp apparatus and are uncorrected. A Bruker IBM 200 NMR spectrometer was used for the 200-MHz 'HNMR spectra. The 270-MHz ' H NMR and the 67-MHz I3CNMR spectra were obtained on a Bruker IBM 270 NMR spectrometer. The 300-MHz 'HNMR and the 75-MHz I3C

(21) (a) Brady, W. T.; Giang, Y.F. J . Org. Chem. 1985,50, 5177. (b) Brady, W. T.; Marchand, A. P.; Giang, Y. F.; Wu, A.-H. Synthesis 1987, 395. (22) Rey, M.; Roberts, S.M.; Dreiding, A. S.;Roussel, A.; Vanherde, H.; Toppet, S.;Ghosez, L. Helo. Chem. Acta 1982, 65, 703. (23) Fischer, H. Angew Chem., h i . Ed. Engl. 1983, 22, 874.

Reaction o j Chromium Carbene Complexes with Olefins

J . Am. Chem. SOC.,Vol. I 1 2, No. I I , 1990 4369

purification (petroleum ether/Et20, 9:l), 80 mg (0.42 mmol, 42%, 1O:l anti/syn) of 3s as a colorless oil was obtained. anti-3a: 'H NMR (270 MHz, CDCI,) 6 7.40-7.20 (m,5 H, Ar), 3.90 (t, 1 H, J3,4= J,,,, = 10.3 Hz, H-3), 3.50 (s, 3 H, OMe), 3.20 (dd, 1 H, J4,4t= 17.3, J4,) = 10.3 Hz, H-4), 2.98 (dd, 1 H, J4.4, = 17.2, J4,,, = 10.2 Hz, H-4'), 1.01 (s, 3 H, Me); I3C NMR (75 MHz, CDC13) 6 208.01 (CO), 137.06 (ipso), 128.43, 127.58, 126.72, 95.33 (C2), 52.71 (OMe), 41.87 (C4), 38.43 (C3), 16.42 (Me); IR (CDCI,) Y 1778 (CO) cm-I; high-resolution mass spectrum calcd for ClzH1402190.0994, Mt - CHI 175.0759, found 175.0762. 3-(Acetoxymethyl)-2-methoxy-2-methylcyck1butan-l-one (3b). From 500 mg (2.00 mmol) of 1 and 1.08 mL (10.00 mmol) of allyl acetate in 30 mL of EtzO after irradiation for 24 h and flash chromatography (petroleum ether/Et20, 6:4), 116 mg (0.62 mmol, 31% 1O:l anti/syn) of 3b was obtained as a colorless oil. anti-3b: IH NMR (300 MHz, CDCI,) 6 4.33 (dd, 1 H, Jgcm= 11.5, J C H 2 , 6.4 Hz, CHZO), 4.21 (dd, 1 H, Jecm= 11.6, JCH2,) = 7.5 Hz, CHz0),'3.34 (s, 3 H, OMe), 2.93 (dd, 1 H, J434t = 15.6, J4,3= 9.8 Hz, H-4), partly overlapping 2.88 (m,1 H, H-3), 2.65 (dd, 1 H, J4P.4 = 15.6, J 4 t . j = 7.6 Hz, H-4'), 2.07 (s, 3 H, Me-CO), 1.34 (s, 3 H, Me); "C NMR (75 MHz, CDCI,) 6 207.06 57.21 (OMe), 43.03 (CO), 170.80 (MeCO), 93.49 (C2), 63.60 (CH,O), (C4), 33.52 (C3), 20.81 (Me), 14.04 (Me); IR (film) Y 1783 (CO), 1741 (OCO) cm-I; MS (EI) 144 (M" - 42). Anal. (C9HI4O4)C, H. 2-Methoxy-53,4-tri~thylcyclobutan-2-one(3c). Through a test tube containing 300 mg (1.20 mmol) of 1 in IO mL of MeCN was bubbled cis-2-butene for IO min. The tube was sealed, irradiated for 19 h, filtered through Celite, and air oxidized for 30 h. The brown precipitate was filtered, and the solvent was removed on a rotary evaporator at water (styryI)carbene]~hromium(O),~~ pentacarbonyl[(ethoxy)(methyl)carbaspirator pressure to give 230 mg of a yellow oil and solid Cr(C0)6. The ene]chromi~m(O),~~ pentacarbonyl[(benzyloxy)(methyl)carbene]chrocrude mixture was evaporatively distilled to give 100 mg (0.70 mmol, mium(0),I6 pentacarbonyl(tetrahydrofurany1-1-carbene)chromi~m(O),~~ 59%) of a colorless oil consisting of an inseparable mixture of 5:l:l pentacarbonyl[ (methyl) [ (tetramethylammonio)oxy]carbene]chromiumanri:syn-Jc/syn:syn-3c/anttanti-3d.anttsyn-3c: IH NMR (300 MHz, (0),36and trans-2-(2-propenyl)- 1 -cyclohexanol.I2 CDCI,) 6 3.55 (qd, 1 H, J4.3 = 11.7, J ~ , M 7.7 ~ Hz, H-4), 3.29 (s, 3 H, Intermolecular Reactions. Method A. To a solution of 1.0 mmol of OMe), 2.54 (qd, 1 H, J3c = 11.7, J3,Mc = 7.5 Hz, H-3), 1.13 (s, 3 H, the carbene in 20 mL of diethyl ether in a 40-mL Fischer Porter pressure Me-C2), 0.97 (d, 3 H, JMc.4 = 7.7 Hz, Me-C4), 0.91 (d, 3 H, J M ~ = , , 7.5 tube was added 5.0 mmol of alkene with a syringe. The solution was Hz, Me-C3); 13C NMR (75 MHz, CDC13) 6 212.34 (CO), 94.89 (C2), saturated with C O (3 cycles to 90 psi of CO) and irradiated (450-W 53.1 1 (C4), 52.73 (OMe), 34.22 (C3), 12.52 (Me), 9.72 (Me), 8.45 Conrad-Hanovia 7825 medium-pressure mercury lamp, Pyrex well) un(Me); IR (CHCI,) Y 1773 (CO) cm-I; high-resolution mass spectrum der 90 psi of C O overnight. The colorless solution was removed by pipet calcd for C8HI5O2(M'H') 143.1073, found 143.1075. from precipitated Cr(C0)6 and the solvent was removed on a rotary 2-Methoxy-2,3,4-trimethylcyck1butan-2-one (3d). From 250 mg (1 .OO evaporator at water aspirator pressure to give a white crystalline residue. mmol) of I after irradiation for 17 h and flash chromatography (petroThe residue was triturated with a few milliliters of petroleum ether, and leum ether/Et20, 8:2), 22 mg (0.15 mmol, 15%) of a colorless oil conthe solution was put on a I5 X 2 cm silica gel column (flash chromasisting of an inseparable mixture of 5: 1 :1 anfi:onti-3d/syn:onti-3d/ tography) and eluted with petroleum ether/ether to give pure cycloanttsyn-3c was obtained. anttanti-3d: ' H NMR (300 MHz, CDCIJ butanone. Isomer ratio was determined by 'H NMR and confirmed by 6 3.32 (s, 3 H, OMe), 2.57 (qd, 1 H, J4,3= 9.6, J4,Mc = 7.0 Hz, H-4), GLC. In some cases the product was further purified by evaporative = 6.8 ~ Hz, H-3), 1.28 (s, 3 H, Me-C2), 2.07 (qd, 1 H, J3,4 = 9.6, J ~ . M distillation. 1.23 (d, 3 H, J M C , 3 = 6.8 Hz, Me-C3), 1.14 (d, 3 H, Jh(e.4 = 7.1 Hz, Method B. The carbene (4.0 mmol) was placed in a Pyrex test tube Me-C4); "C NMR (75 MHz,CDCI,) 6 212.18 (CO), 91.68 (CZ), 52.97 which was sealed with a rubber septum, evacuated, and purged with (OMe), 52.09 (C4), 37.32 (C3), 14.96 (Me), 13.65 (Me), 12.01 (Me); argon (three times). A solution of 20.9 mmol of alkene in 40 mL of IR (film) Y 1776 (CO) cm-I; MS (CI, NH,): 160 (M + NH4'), 143 (M degassed acetonitrile was added with a syringe, and the resulting orange + H'). Anal. (C8HI6O2)C, H. solution was irradiated overnight (450-W Conrad-Hanovia 7825 medil-Methoxy-l-methylspiro[3.5]nonan-2-one(3e). From 250 mg (1 .OO um-pressure mercury lamp, Pyrex well). The solvent was removed on mmol) of 1 and 600 WL(5.00 mmol) of methylenecyclohexane after a rotary evaporator at water aspirator pressure. The yellow solid residue irradiation for 21 h and flash chromatography (petroleum ether/Et20), was dissolved in ethyl acetate, filtered through Celite, diluted with one 87 mg (0.48 mmol, 48%) of an inseparable 15:l mixture of 3e and spiro volume of hexane, and air oxidized overnight in a light box (6 X 20 W 3e' was obtained as a colorless oil. Spiroketone 3e: 'H NMR (300 MHz, Vitalite fluorescent bulbs). Filtration, through Celite, of the brown CDCI,) 6 3.39 (s, 3 H, OMe), 2.63 (d, 1 H, J,,,, = 16.8 Hz, H-3), 2.59 suspension and solvent removal on a rotary evaporator gave almost pure (dd, 1 H, JY,, = 16.8, J = 1.1 Hz, H-3'), 1.75-1.43 (m,7 H, CHI), product. The sample was further purified, for elemental analysis, by 1.32-1.17 (m, 3 H, CHI), superimposed on 1.30 (s, 3 H, Me); I3C NMR evaporative distillation. (75 MHz, CDC13) 6 209.04 (CO), 92.46 (CI), 53.06, 51.12, 40.00, 32.83, 2-Methoxy-2-methyl-3-phenylcyclobutan-l-one (34. From 250 mg 30.52, 25.80, 23.81, 22.77, 12.80 (Me); IR (film) Y 1778 (CO) cm-I; MS (1 .00 mmol) of pentacarbonyl[(methoxy)(methyl)carbene]chromium(O) (El) 182 (M'). Anal. (Cl,HI8O2)C, H. (1) and 570 pL (5.00 mmol) of styrene after irradiation for 22 h and 2-Methoxy-2,3,3,4-tetramethylcyclobutan-l-one (3f). From 750 mg (3.00 mmol) of 1 and 1.67 mL (15.00 mmol) of 2-methyl-2-butene after irradiation for 31 h and flash chromatography eluting first with 20 mL of petroleum ether and then with 50 mL of petroleum ether/Et20 (9:l), (24) Wittig, G.; Schollkopf, U. Chem. Ber. 1954, 87, 1318. 359 mg (2.30 mmol, 7 1%) of almost pure 3f as a colorless oil was ob(25) Organic Syntheses; Wiley: New York, 1963; Collect. Vol. IV, 476. tained. The oil was evaporatively distilled to give 296 mg (1.90 mmol, (26) Ben-lshai, D.; Giger, R. Tetrahedron Lerr. 1965, 8, 4523. 63%) of 3f IH NMR (300 MHz, CDCI,) 6 3.42 (q, 1 H, J = 7.3 Hz, (27) Fieser and Fieser, Reagents in Organic Synthesis; 1967, p 706. H-4), 3.33 (s, 3 H, OMe), 1.23 (s, 3 H, Me), 1.13 (s, 3 H, Me), 0.97 (d, (28) Organic Syntheses; Wilcy: New York, 1955; Collect. Vol. 111, 506. (29) Crandall. J. K.: Keyton. D. J.: Kohne, J. J . Org. Chem. 1968, 33, 3 H, J = 7.3 Hz, Me-C4), 0.89 (s, 3 H, Me); I3C NMR (75 MHz, 3655. CDCI,) 6 210.65 (CO), 94.89 (C2), 61.42 (C4), 53.90 (OMe), 38.41 (30) Fischer, E. 0.;Aumann, R. Chem. Ber. 1968. 101, 960. (C3), 20.89 (Me), 19.32 (Me), 10.54 (Me), 7.38 (Me); IR (ilm) Y 1772 (31) Conner, J. A.; Jones, E. M. J . Chem. Soc., Dulron Trans. 1973,2119. (CO) cm-'; MS (El) 156 (M"). Anal. (C9H1602) C, H. (32) Yamashita, A. (Upjohn), Eur. Pat. Appl. EP 146,348. 7-Methoxy-7-methylbicyclo[3.2.O]hept-2-en-6-one (5). From 500 mg (33) Aumann, R.; Heinen, H. Chem. Ber. 1987, 120, 537. (2.00 mmol) of 1 and 825 pL (10.00 mmol) of cyclopentadiene after (34) (a) Fischer, E. 0.; MaasMI, A. J . Organomer. Chem. 1968,12, 15. irradiation for 20 h and flash chromatography (petroleum ether/Et20, (b) Darensbourg. M. V.; Darensbourg, D. J. Inorg. Chem. 1970, 9, 32. 9:l). 205 mg (1.34 mmol, 67%, 1O:l exo/endo) of 5 was obtained as a (35) Dots, K. H.; Sturm, W.; Alt, H. G. Organometallics 1968,6, 1424. colorless oil. exo-5: 'H NMR (300 MHz, CDCI,) 6 5.80 (qd, 1 H, J3.2 (36) Fischer, E. 0.;MaasMl, A. Chem. Ber. 1967, 100, 2445. (37) Hegedus, L.S.; McKearin, J. M. J . Am. Chem. Soc. 1982, 104,2444. = 5.8, J , , , = J3,4 = J3,4, = 1.9 Hz, H-3), 5.61 (apparent qd, 1 H, J2.3 =

NMR spectra were obtained on a Bruker ACS-300 NMR. NMR spectra were recorded in CDC13, and chemical shifts are given in ppm relative to Me@ (0 ppm, IH), CHCI, (7.26 ppm, 'H), or CDCI3 (77 ppm, I3C) unless otherwise specified. Assignments in the "C NMR spectra (broad band) are based on comparison in the measured substance class. IR spectra were recorded on a Beckmann 4240 spectrophotometer. Electron-impact (El) and chemical-ionization (CI) mass spectra were obtained on a V. G . Micromass Ltd., Model 16F spectrometer. Optical rotations were obtained on a Perkin-Elmer 24 polarimeter at a wavelength of 589 nm (sodium D line) by a 1.0-dm cell with a total volume was reported in degrees per decimeter of 1 mL. Specific rotation, [a]0, at the specified temperature, and the concentration (c), given in grams per 100 mL in the specified solvent. For the purification of crude reaction mixtures, radial-layer (Chromatotron Model 7924) and column chromatographic techniques were applied in most cases. Merck silica gel 60 P F (for radial-layer chromatography) and Merck silica gel (230-400 mesh) or Alfa activated, neutral aluminum oxide (for column chromatography) were used as stationary phases. Elemental analyses were performed by M-H-W Laboratories, Phoenix, AZ. The following chemicals were prepared according to literature procedures: methylene~yclohexane,2~ cy~lopentadiene,2~ N-vinylacetamide,26 N-cyclohex- 1-enylm~rpholine,~'ketene diethyl acetal,2s 3-methyl- 1,2[(methoxy)(methyl)carbene]chromium(0),30 b ~ t a d i e n e ?pentacarbonyl ~ pentacarbonyl[(cyclopropyl)(methoxy)carbene]chromium(O)~1 pentacarbonyl[(n-butyl)(methoxy)carbene]chr~mium(O),~~ pentacarbonyl[ (methoxy)(phenyl)~arbene]chromium(O),~pentacarbonyl[(methoxy)-

4310 J . Am. Chem. SOC.,Vol. 112. No. 1 1 , 1990

Soderberg et al.

irradiation for 24 h and flash chromatography (petroleum ether/Et20, 5.7, 52,' J2.4 J2.4' = 2.3 Hz, H-2), 3.93 (ddd, I H, J5.4, = 9.5, J5,' = 8.1, J5,4= 1.4 Hz, H-5), 3.33 (m, 1 H, H-I), 3.25 (s, 3 H, OMe), 2.55 95:5), 203 mg (0.91 mmol, 96%. 14:l exo/endo) of 7f as a colorless oil. = 17.3 Hz, H-4), 2.35 (qdd, 1 H, J4,,4= 17.3,J4g,s= 9.5, (dm, I H, J4,4, exo-7f 'H NMR (300 MHz, CDCI3) 6 5.95 (td, 1 H, J3,2 = 10.3, Jl,4 = 4.0 Hz, H-3), 5.85 (dd, I H, J2.j = 10.4, J2.1 = 4.3 Hz, H-2), 3.77 J4,,, = J4,.2 = J4,,, = 2.1 Hz, H-4'), 1.07 (s, 3 H, Me); 'IC NMR (75 MHz, CDCIj) 6 212.05 (CO), 134.62, 128.58, 97.34 (C7), 58.89 (C5), (ddd, 1 H, 56.1 = 10.6, 56.5 = 6.5, J6.5' = 4.1 Hz, H-6), 3.48 (12 line m, 52.63 (OMe), 50.84 (CI), 34.34 (C4). 12.03 (Me); IR (film) v 1777 2 H, J = 7.1 Hz, OCH2). 2.87 (m,1 H, H-I), 1.95 (m, 2 H), 1.79-1.22 (CO) cm-I; MS (El) 152 (M'). Anal. (CPHI4O2)C, H. (m,8 H), 1.19 (t. 3 H, J = 7.0 Hz, OCH2CHl), 0.90 (t, 3 H, J = 7.0 8-Methoxy-8-methylbicyclo(4.2.O@t-2-en-I-one(7a). From 250 mg Hz, Me); I3C NMR (75 MHz, CDCI,) 6 21 1.75 (CO), 130.52, 124.54, (1 .OO mmol) of 1 and 470 p L (5.00 mmol) of 1,3-cyclohexadiene after 97.31 (C8), 60.32 (OCH,), 53.59 (C6), 36.44 (CI), 26.30, 24.85, 22.89, 21.26, 18.88, 15.51, 13.84; IR (film) Y 1770 (CO) cm-') MS (El) 222 irradiation for 26 h and flash chromatography (hexane/Et20, 95:5), 86 mg (0.52 mmol,52%, 14:l exo/endo) of 7n was obtained as a pale yellow (M'). Anal. (C14H2202)C, H. oil. exo-7% 'H NMR (270 MHz, CDCI,) 6 5.98 (m, 1 H, H-3), 5.83 8-(Benzyloxy)-8-methylbicyclo(4.2.O~t-2-en-7-one (7g). From 326 = 4.2 Hz, H-2), 3.79 (m,1 H, H-6), 3.36 (s, (dd, 1 H, J2,, = 10.2, J231 mg (1 .OO mmol) of 6g and 470 p L (5.00 mmol) of 1,3-cyclohexadiene 3 H, OMe), 2.91 (dd. 1 H, J1.6 = 10.7, J,,2 = 4.3 Hz, H-I), 2.05-1.85 after irradiation for 23 h and flash chromatography (hexane/Et20, 9:l), (m, 3 H, H-4, H-5). 1.61 (m, 1 H, H-5'), 1.17 (s, 3 H, Me); lJC NMR 153 mg (0.63 mmol,63%) of exo-7g followed by 16 mg (0.07 mmol,7%) (67.5 MHz, CDCIj) 6 210.98 (CO), 130.33, 124.71, 95.27 (C8), 53.88 of endo-7g was obtained as colorless oils. exo-7g: IH NMR (270 MHz, (OMe), 52.60 (C6), 36.29 (CI), 21.30 (C4), 19.00 (C5), 13.03 (Me); CDCI,) 6 7.29 (m.5 H, ArH), 5.96 (td, 1 H, Jl,2= 10.3, Jl,4= 3.8 Hz, IR (film) Y 1770 (CO) cm-'; MS (Et) 166 (M+). Anal. (C10H1402) C, H-3), 5.82 (ddd, 1 H, J2.j = 10.4, J2.1 = 4.4, J2.4 = 2.2 Hz, H-2), 4.58 H. (d, 1 H, Jsnn = 11.1 Hz, ArCH2), 4.52 (d, 1 H, JBcm= 11.1 Hz, ArCH2), 8-Cyclopropyl-8-methoxybicyclo(4.2.O@t-2-en-7-one (7b). From 422 3.84 (ddd, I H, 16.1 10.7, J 6 , 5 = 6.4, J6.3 = 4.2 Hz, H-6), 2.96 (ddd, mg (1.53 mmol) of 6b and 610 p L (7.64 mmol) of 1,3-cyclohexadiene 1 H, J1,6 = 10.7, J 1 , 2= 3.9, J = 1.5 Hz, H-I), 1.96 (m,3 H, H-4, H-5), after irradiation for 45 h and flash chromatography (petroleum ether/ 1.58 (m,1 H, H-5'), 1.30 (s, 3 H, Me); I3C NMR (67 MHz, CDCI,) Et20, 95:5), 141 mg (0.73 mmol,48%) of 7b was isolated as a colorless 6 210.89 (CO), 138.22 (ipso), 130.46, 128.28, 127.51, 124.68.95.35 (C8), oil. Only the exo isomer was observed: IH NMR (300 MHz, CDCI,) 67.59 (OCH2), 54.14 (C6), 36.84 (CI), 21.34, 19.00, 13.90; IR (film) 6 5.88 (m, 2 H, H-2, H-3), 3.54 (m, 1 H, H-6), 3.35 (s, 3 H, OMe), 2.84 Y 1770 (CO) cm-I; MS (EI) 242 (M'). Anal. (C16H1802) C, H. (dd, 1 H, J1.6 = 10.6, Jl,2= 2.8 Hz, H-I), 1.85 (m,3 H, H-4, H-5), 1.55 endo-7g: 'H NMR (270 MHz, CDCI,) 6 7.40-7.25 (m,5 H, ArH), (m, I H, H-5'1, 0.82 (m, 1 H, cyclopropyl), 0.68 (m,1 H, cyclopropyl), 5.96 (m,2 H, H-2, H-3), 4.80 (d, 1 H, J = 11.0 Hz, ArCH,), 4.67 (d, 0.43 (m, 2 H, cyclopropyl), 0.29 (m, I H, cyclopropyl); 'IC NMR (75 1 H, J = 11.1 Hz. ArCH,), 3.47 (m, 1 H, H-6), 2.88 (dd, 1 H, J1.6 = MHz, CDCI,) 6 210.24 (CO), 129.56, 125.00, 97.17 (C8), 53.49, 53.18, 9.6, J1,2= 3.4 Hz, H-I), 2.05 (m,4 H, H-4, H-5), 1.54 (s, 3 H, Me); 36.64 (CI), 21.35, 18.82, 10.10, 2.09, 1.46; IR (film) v 1765 (CO) cm-I; I3C NMR (75 MHz, CDCI,) 6 21 1.96 (CO), 138.64 (ipso), 131.54, MS (El) 192 (M'). Anal. (CI2HI6O2)C, H. 128.20, 127.25, 124.11, 91.19 (C8), 67.62 (OCHZ), 49.69 (C6), 37.65 8-n-Butyl-8-methoxybicyclo(4.2.0@t-2-en-7-0~ (7c). From 320 mg (CI), 21.36, 21.17, 18.14; IR (film) v 1765 (CO) cm-I; MS (EI) 242 (1.10 mmol) of 6c and 520 p L (5.50 mmol) of 1,3-cyclohexadiene after (M'). Anal. (CI6Hl8O2):C, H. irradiation for 19 h and flash chromatography (petroleum ether/Et20, 8-Methyl-8-[(timethylsilyl)oxy~icyclo(4.2.O~t-2-en-7-0~ (7h). To 95:5), 105 mg (0.50 mmol,46%, 13:l exo/endo) of 7c was obtained as 618 mg (2.00 mmol) of pentacarbonyl[(methyI)[(tetramethyla colorless oil. exo-7c: ' H NMR (300 MHz, CDCI,) 6 5.91 (td, 1 H, ammonio)oxy]carbene]chromium(0)in 30 mL of Et20, under argon 3.4 Hz, H-3), 5.82 (dd, 1 H, J2,j = 10.3, J2.l Jj.2 = 10.5, J j , 4 = J3,4, atmosphere at -20 "C was added with a syringe 280 p L (2.20 mmol) of 4.3 HZ, H-2), 3.71 (ddd, I H, J6,1 = 10.6, J6.5 = 6.3, J6.3 = 4.3 Hz, chlorotrimethylsilane. The reaction mixture was stirred for 1 h at -20 H-6), 3.27 (s, 3 H, OMe), 2.83 (dd, 1 H, J1.6 = 10.6, J I 2 = 4.0 Hz, H-I), OC, saturated with C O (3 cycles to 90 psi), and irradiated at ambient 1.98-1.84 (m, 3 H). 1.77-1.19 (m, IO H), 0.87 (t, 3 H, J = 7.0 Hz, Me): temperature for 17 h at 90 psi of CO. The precipitate formed was 'IC NMR (75 MHz, CDCI,) 6 21 1.60 (CO), 130.68, 124.50,97.68 (C8), removed by filtration through Celite, the Celite was washed with 30 mL 53.67, 52.61, 36.18 (CI), 25.75, 24.76, 22.93, 21.30, 18.96, 13.88; IR of Et,O, and the solvent was removed on a rotary evaporator a t water (film) Y 1775 (CO) cm-I; MS (El) 208 (M+). Anal. (CI3HmO2)C, H. aspirator pressure. The crystalline residue was triturated with ca. 3 X 8-Methoxy-8-phenylbicyclo(4.2.Oloct-2-en-7-one (7d). From 203 mg 1 mL of petroleum ether and filtered through a disposable pipet filled (0.65 mmol) of 6d and 305 p L (3.25 mmol) of 1,3-cyclohexadiene after with 3 cm of silica gel, and the silica was washed with petroleum ether irradiation for 42 h and flash chromatography (petroleum ether/Et20, (20 mL). The solvent was removed (rotary evaporator) to give an oil that 95:5), 1 1 I mg (0.49 mmol, 75%) of 7d was obtained as colorless crystals. was immediately flash chromatographed (16 X 2 cm column, petroleum Only exo-7d was isolated: mp 52-54 OC; 'H NMR (300 MHz, CDCI,) ether/Et20, 95:5) to give 164 mg (0.73 mmol, 37%, 5:l exo/endo) of 7h 6 7.31 (m, 5 H, ArH), 5.96 (m, 1 H, H-3), 5.25 (m,1 H, H-2), 4.02 (ddd, as a colorless oil. exo-7h: 'H NMR (300 MHz, CDCI,) 6 5.85 (m, 2 9.7, 56.5 = 6.3, 56.5' = 3.4 HZ, H-6), 3.17 (S, 3 H, OMe), 3.09 I H, J 6 , l H, H-2, H-3), 3.78 (ddd, 1 H, J6.1 = 10.9, Jb5 = 6.3, J65' = 5.5 Hz, H-6), (m, 1 H, H-I), 2.10-1.93 (m. 3 H, H-4, H-5), 1.58 (m,1 H, H-5'); 'IC 2.67 (ddd, 1 H, J1,6 = 10.9, J1,2= 3.8, J = 1.9 Hz, H-I), 1.94-1.78 (m, NMR (75 MHz, CDCI,) 6 209.40 (CO), 134.29 (ipso), 130.14, 128.05, 3 H, H-4, H-5'), 1.59 (qd, 1 H, J5.5, = 13.5 Hz, J 5 4 = J5,4t = J5.6 = 6.8 128.01, 127.48, 124.85, 97.90 (C8), 54.56, 54.30, 39.33 (CI), 21.11, Hz, H-5), 1.18 (s, 3 H, Me), 0.1 1 (s, 9 H, SiMe,); IJC NMR (75 MHz, 18.60 IR (film) v 1775 (CO) cm-I; MS (El) 228 (M+). Anal. (CISCDCIJ 6 212.60 (CO), 129.99, 124.73, 91.96 (C8), 54.61 (C6), 39.18 H1602) C. H. (CI), 21.44, 19.13, 18.85, 1.46 (3C, SiMe,); IR (film) v 1779 (CO) cm-I; 8-Ethoxy-8-methylbicyclo(4.2.O~ct-2-en-7-one (7e). From 264 mg MS (El) 224 (M'). Anal. (CI2H2,,O2Si) C, H. ( I .OO mmol) of 6e and 470 p L (5.00 mmol) of 1,3-cyclohexadiene after Spiro(bicyclo(4.2.0~ct-2-ene-8,I'-2'-oxacyclopentane]-7-one (7j) and irradiation for 22 h and flash chromatography (petroleum ether/Et20, Spi~bicych(4.1.0~-2-ene-7,1'-2'-o~cyclopentane] (8). From 262 mg 9:l), 138 mg (0.77 mmol,77%) of exe7e followed by 14 mg (0.08 mmol, (1.00 mmol) of 6j and 470 pL (5.00 mmol) of 1,3-cyclohexadiene after 8%) of endo-7e was obtained as colorless oils. exo-7e: 'H NMR (300 irradiation for 50 h and flash chromatography (petroleum ether/Et20, MHz, CDCIJ 65.87 (td, 1 H, J = ca. IO, J2.3 = ca. 4 Hz, H-3), 5.74 9:l), 17 mg (0.1 1 mmol,11%) o f 8 followed by 97 mg (0.55 mmol, 5576, (ddd, 1 H, J2.3 = 10.2, J2,1= 4.3, J2.4 = ca. 2 Hz, H-2), 3.71 (ddd, 1 H, I5:l exo/endo) of 7j was obtained as colorless oils. exo-7j: 'H NMR J6,1 = 10.7. J6.5 = 6.2, J6.5' = 4.5 Hz, H-6), 3.46 (12 line, 2 overlapping (300 MHz, CDCI,) 6 5.94 ( 1 1 line m, I H, J3.2 = 10.1, = 5.7, J3,4, qd, 2 H, Jpm = 9.0, J = 7.0 Hz, OCHZ), 2.80 (ddd, I H, 11.6 = 10.6, J l , 2 4.2, J3,l = 1.8 Hz, H-3), 5.80 (tdd, 1 H, J2.j = 10.1, J2,1 = 4.1, J2.4 = 4.3, Jl,4 = 1.5 Hz, H-I), 1.93-1.80 (m,3 H, H-4, H-5), 1.52 (m,1 = 52.4' = 2.0 Hz, H-2), 3.95-3.79 (m,2 H, H-3'), 3.45 (td, 1 H, J6,1= H, H-57, 1 .I 3 (s, 3 H, Me), 1 .I 1 (t, 3 H, J = 7.0 Hz, CH2CH,); 10.4, J6.5 = 56.5' = 7.1 HZ, H-6), 2.88 (10 line m, 1 H, J1.6 = 10.4, J l . 2 NMR (75 MHz, CDCIj) b 211.64 (CO), 130.21, 124.71, 94.78 (C8), = 4.2, J1.4 = J1.4, = 1.7 Hz, H-I), 2.00-1.76 (m,6 H), 1.69 (m, 2 H); 60.60 (OCH,), 53.79 (C6), 36.54 (Cl), 21.25, 18.92, 15.63, 13.76; IR 'IC NMR (75 MHz, CDCI,) 6 214.37 (CO), 130.23, 124.06,99.33 (C8), (film) Y 1775 (CO) cm-I; MS (El) 180 (M'). Anal. (CllHI6O2)C, H. 69.26 (C3'), 52.55 (C6), 36.83 (CI), 28.44, 25.76, 21.52, 19.20; IR (film) endo-7e: 'H NMR (300 MHz, CDCI,) 6 5.93 (m, I H, H-3), 5.82 v 1778 (CO) cm-I; MS (El) 178 (M+). Anal. (CllH1,02) C, H. (m, 1 H, H-21, 3.70 (qd, 1 H, Jgm = 9.0, J = 7.0 Hz, OCH2), 3.54 (qd, 8: ' H NMR (300 MHz, CDCI,) 6 5.86 (m,1 H, H-3), 5.68 (m,1 1 H, JIem= 9.0, J 7.0 Hz, OCH,), 3.40 (ddd, 1 H, 56.1 = 9.3, J6,5 = H, H-2), 3.85 (m, 1 H, H-3'), 3.67 (m, 1 H, H-3'), 2.03-1.76 (m, 7 H), 6.0, J6.5' = 3.0 Hz, H-6), 2.76 (m, 1 H, H-I), 2.1 1-1.92 (m,3 H, H-4, 1.58 (m,1 H), 1.26 (m,2 H); 'IC NMR (75 MHz, CDCI,) 6 125.66, H-5).1.59-1.50(m,l H,H-5'),1.50(s,3H,Me),1.15(t,3H,J=7.1 122.02, 73.22 (C7), 68.53 (C3'), 33.61, 24.92, 22.72, 21.51, 21.38, 16.12; Hz, CH2CHI); "C NMR (75 MHz, CDCIj) 6 211.90 (CO), 129.83, IR (film)Y 3028,2923,2862, 1642, 1456, 1137, 1066, 1026, 1003,929, 123.91,91.15 (C8), 60.91 (OCH2),49.47 (C6), 37.43 (CI), 21.10, 21.01, 716 cm-I; MS (El) 150 (M'). Anal. (CloH140)C, H. 18.10, 15.74; IR (film) Y 1770 (CO) cm-I; MS (El) 180 (M'). Anal. (CiiHi602) c, H. Similar amounts and procedures as described above but without C O 8-n-Butyl-8-ethoxybicyclo(4.2.Oloct-2-en-7-one (71). From 292 mg atmosphere irradiated for 122 h gave after chromatography 41 mg (0.27 (0.95 mmol) of 61 and 470 p L (5.00 mmol) of 1,3-cyclohexadiene after mmol, 27%) of 8 followed by 27 mg (0.15 mmol, 15%) of 7j.

Reaction of Chromium Carbene Complexes with Oleflns 3-Ethoxy-2-methoxy-2-methylcyclobutan-l-one (loa). From 1 .OO g (4.00 mmol) of I and 2.00 mL (20.9 mmol)of ethyl vinyl ether in 40 mL of degassed MeCN (method B) after irradiation for 14 h followed by air oxidation for 18 h and after filtration through Celite, 550 mg (3.78 mmol, 87%. 6:l anti/syn) of 10a was obtained as a pale yellow oil. anri-loa: 'H NMR (300 MHz, CDCI,) 6 4.18 (dd, 1 H, J3,4= 8.1, J,,4, = 7.6 Hz, H-3), 3.55 (q, 1 H, J = 7.1 Hz, OCH,), overlapping 3.53 (9. 1 H, J = 7.0 Hz, OCH,), 3.35 (s, 3 H, OMe), 2.93 (dd, 1 H, J4,4,= 17.9, J4,, = 8.4 Hz, H-4), 2.79 (dd, I H+J4,,4= 17.9, J4e.3 = 7.4 Hz, H-4'), 1.35 (s, 3 H, Me), 1.20 (t, 3 H, J = 7.0 Hz, CH2CH3); "C NMR (75 MHz, CDClj) 6 207.61 (CO), 95.08 (C2), 71.06 (C3), 65.99 (OCHZ), 52.61 (OMe), 46.62 (C4), 15.10 (Me), 13.45 (Me); IR (film) Y 1783 (CO) cm-I: high-resolution mass spectrum calcd for C8H1403158.0943, found 158.0936. 3-Acetoxy-2-methoxy-2-methylcyclobutan-l-one (lob). From 250 mg (1.00 mmol) of 1 and 460 p L (5.00 mmol) of vinyl acetate in 20 mL of E t 2 0 after irradiation for 23 h and evaporative distillation, 32 mg (0.19 mmol, 19%) of 10b was obtained as a colorless oil. A ca. 90% purity was obtained (GLC), further purification was not possible: 'H NMR (300 MHz, CDCIj) 6 5.33 (dd, I H, 13.4 = 8.8,53,4t 7.1 Hz, H-3). 3.37 (s, 3 H. OMe), 3.19 (dd, 1 H, J4,41= 18.5, J4,3= 8.8 Hz, H-4). 2.92 (dd, 1 H, J4t4 = 18.5, J48.3 = 7.1 Hz, H-4'), 2.12 (s, 3 H, MeCO), 1.35 (s, 3 H, Me); I3C NMR (75 MHz, CDCI,) 6 205.90 (CO), 170.26 (MeCO), 14.05 95.07 (C2). 65.78 (C3), 52.76 (OMe), 46.94 (C4), 20.58 (MeCO), (Me); IR (film) Y 1790 (CO), 1748 (OCO) cm-'. J-(N-Acetylamiw)-t-methoxy-2metbyIcyclob(1Oc). From 250 mg ( 1 .OO mmol) of 1 and 425 mg (5.00 mmol) of N-vinylacetamide after irradiation for 24 h followed by flash chromatography eluting with first 40 mL of hexane and then 100 mL of Et,O gave 341 mg (4.0 mmol) of N-vinylacetamide and then eluting with 200 mL of CH,CI,/MeOH (8:2) gave 165 mg (0.95 mmol, 96% 8:l anti/syn) of almost pure 1Oc. The product was further purified by evaporative distillation to give 131 mg (0.77 mmol, 77%, 8:l anti/syn) of 1Oc as a colorless oil. mi-l0c: 'H NMR (270 MHz, CDCIj) 6 6.60 (d, 1 H, = 6.8 Hz, NH), 4.66 (4, 1 H, J = 8.7, H-3), 3.34 (s, 3 H, OMe), 3.08 (dd, 1 H, J4,4,= 18.0, J4.3 = 9.9 HZ, H-4). 2.83 (dd, 1 H, J4,,4 = 18.1, J4,,3 8.6 Hz, H-4'), 2.01 (s, 3 H, Me-CO), 1.27 (s, 3 H, Me); I3C NMR (75 MHz, CDCI,) 6 207.09 (CO), 170.48 (NCO), 95.08 (C2), 52.60 (OMe), 45.82 (C4), 44.04 (C3), 22.96 (MeCO), 14.21 (Me): IR (CHCI,) u 1787 (CO), 1679 (NCO) cm-I: high-resolution mass spectrum calcd for C,H,,NO, 171.0896, found 171.0892. 2-Methoxy-2-methyl-~(2-oxo-l-pyrrolidinyl)cyclobutan-l-one (1Od). From 250 mg ( I .OO mmol) of 1 and 565 p L (5.00 mmol) of N-vinyl-2pyrrolidone after irradiation for 40 h followed by flash chromatography eluting with first 75 mL of E t 2 0 and then Et20/MeOH (9:l), 155 mg (0.78 mmol, 78% 7:l anti/syn) of 1Od was obtained as a colorless oil. anti-1W: IH NMR (300 MHz, CDCI,) 6 4.33 (t, 1 H, J,,4 = J3,4t= 9.8 = 9.2 Hz, H-4). partly overHz, H-3), 3.44 (dd, 1 H, J4,4,= 18.2, .I4,, lapping 3.35 (m, 2 H, NCH2), 3.24 (s, 3 H, OMe), 2.85 (dd, 1 H, J4,4 = 18.1, J4,,,= 10.5 Hz, H-49, 2.29 (apparent dt, 2 H, J , = 8.1, J2 = 2.0 Hz. COCH2), 1.94 (m, 2 H, CH,), 1.16 (s, 3 H, Me); "C NMR (75 MHz, CDCI,) 6 206.01 (CO), 175.62 (NCO), 96.00 (C2), 52.18 (OMe), 47.91 (C3). 46.97 (C4). 41.75 (NCH,), 31.16 (CH,CO), 17.94 (CH,), 13.75 (Me); IR (CHCI,) Y 1790 (CO), 1679 (NCO) cm-I; high-resolution mass spectrum calcd for CloHI5NO, 197.1052, found 197.1049. 8-Methoxy-8-methyl-2-oxabicyclo(4.2.0~-7-~ (1Oe). A test tube containing 1.00 g (4.00 mmol) of 1 and 2.0 mL (21.90 mmol) of 3,4dihydro-2H-pyran in 40 mL of MeCN (method B) was irradiated for 14 h and air oxidized for 30 h. After Celite filtration and distillation 550 mg (3.21 mmol, 80% 11:l exo/endo) of 1Oe was obtained as a colorless oil. exo-lOe: 'H NMR (300 MHz, CDCI,) 6 3.96 (d, 1 H, J1,6= 6.5 Hz, H-I), 3.74 (m, 1 H, H-3), 3.56 (m,1 H, H-3'), 3.22 (s, 3 H, OMe), 2.00 (m, 1 H, H-6), 1.69-1.29 (m, 4 H, H-4 and H-5), 1.20 (s, 3 H, Me); I3C NMR (75 MHz, CDCI,) 6 207.84 (CO), 96.70 (C8), 70.67 (CI), 64.68 (c3), 55.04, 53.12, 21.91 (CH,), 18.27 (CH,), 9.15 (Me); IR (CHCI,) Y 1782 (CO) cm-I; high-resolution mass spectrum calcd for C9H1401170.0943, found 170.0948. 3-Acetoxy-2,3-dimthyl-2-methoxycyclobutan-l-one (lor). From 500 mg (2.00 mmol) of 1 and I .30 mL (10.00 mmol) of 2-acetoxy-I-propene followed by irradiation for 15 h and flash chromatography (petroleum ether/Et,O. 8:2), 62 mg (0.33 mmol, 16%. 1:l syn/anti) of 1Of was obtained together with 8 mg (0.07 mmol, 3%) of 1W as colorless oils. The products were not separable. ami- and syn-lM ' H NMR (270 MHz, CDCI,) 6 3.51 (d, 1 H, J4,43 = 18 Hz, H-4). 3.47 (s, 3 H, OMe), 3.41 (s, 3 H, OMe), 3.24 (d, 1 H, J4.4t= 18.3 Hz, H-4), 3.01 (d, 1 H, J4:4 = 18.2 Hz, H-4'), 3.00 (d, 1 H, J4j.4 = 17.9 Hz, H-4'), 2.10 (s, 6 H, OAc), 1.64 (s, 3 H, Me), 1.59 (s, 3 H, Me), 1.46 (s, 3 H, Me), 1.37 (s, 3 H, Me); 'IC NMR (75 MHz, CDCI,) 6 207.21 (CO), 205.77 (CO), 170.31 (Me-CO), 169.83 (Me-CO), 93.39 (C2). 93.34 (C2), 56.37, 53.92, 53.76, 52.91, 50.32, 38.68, 21.42, 21.37, 19.93, 18.38, 13.65, 13.15;

J . Am. Chem. SOC.,Vol. 112, No. 11, 1990 4371 IR (film) u 1789 (CO), 1746 (OCO) cm-l; MS (El) 158 (M' - CO). Anal. (C9HI4O4)C. H. (S,S,R)-, (S,R,S)-, (S,S,S)-,and (S,R,R)-2,4-Dimethyl-3-ethoxy-2-(menthyloxy)cyclobutan-l-one(lla and llb). From 374 mg ( I .OO mmol) of 12 and 550 pL (5.00 mmol) of ethyl I-propenyl ether (2:l &/trans) in 20 mL of Et,O after irradiation for 23 h and flash chromatography eluting with first petroleum ether then petroleum ether/Et,O (9:l), 218 mg (0.74 mmol, 74%) of the title compounds was obtained as 1 (S,R,R) a colorless oil consisting of a 81 (S,S,R)/S(S,R,S)/3(S,S,~)/ mixture. Spectral data was in complete accordance with literature values.l' Pentacarbonyl[/-(-)-(menthyloxy)(methyl)carbenebhromium(O)( 12). Acetyl bromide (0.40 g, 3.25 mmol) dissolved in 5 mL of CH2CI2was added by syringe to a solution of 1.00 g (3.24 mmol) of pentacarbonyl[(methyl)[(tetramethylammonio)oxy]carbene]chromium(0)in 50 mL of CH,C12, at -40 O C (dry ice/acetone) under argon atmosphere. The resulting deep brown-red solution was stirred a t -40 OC for 30 min followed by the addition of 0.50 g (3.21 mmol) of /-(-)-menthol dissolved in 5 mL of CH,CI,. After 6 h at -40 OC, the reaction mixture was allowed to reach room temperature overnight. The solvent was removed on a rotary evaporator (water aspirator) to give a yellow solid. Hexane was added, and insoluble material was removed by filtration through Celite. The yellow solution was washed with saturated NaHCO, (aqueous) and brine and dried over MgS04(s) followed by solvent removal. The crude yellow oil was flash chromatographed, eluting with hexane to give, after solvent removal, 0.76 g (2.03 mmol, 63%) of 12 as an orange oil: 'H NMR (300 MHz, CDCI,) 6 5.03 and 4.74 (br s, 1 H, rotamers, OCH), 2.96 (br s, 3 H, Me), 2.20-1.05 (m,9 H), 0.96 (br s, 6 H, CHMe,), 0.81 (br s, 3 H, Me); 13C NMR (75 MHz, CDCl,, 2 rotamers) 6 354.73 (Cr=C), 353.74 ( C d ) , 224.19 (trans-CO), 223.20 (rrans-CO), 216.65 (cis-CO), 93.50 (OCH), 87.79 (OCH), 51.16 (CF CMe),47.88 (Cr;=CMe),42.17,41.78,41.24,41.33,41.08, 33.87, 31.11, 26.43, 23.97, 23.07, 22.58, 21.85, 21.36, 16.12, 14.90; IR (film) Y 2045 (trans-CO), 1925 (cis-CO, br) cm-'; MS (CI, NH,) 271 (M - 4 C O + H'), 270 (M' - 4 CO). General Procedure for the Preparation of the Chromium Carbenes 14a-n, 16,20, and 21. In an oven-dried 200-mL Airless flask equipped with a stir bar IO mmol of pentacarbonyl[(tetramethylammonio)carbene]chromium salt was dissolved in 150 mL of methylene chloride. The solution was put under an argon atmosphere and cooled to -40 OC with an acetone/dry ice bath.13 To the faint yellow solution was added 12.00 mmol of either pivaloyl chloride or acetyl bromide by syringe. The reaction mixture was stirred at -35 f 5 "C for 1 h (the color changed slowly to deep red-brown) after which 12.00 mmol of alcohol dissolved in 6 mL of CH2C12was added by syringe. The solution was stirred for 3 h at -35 OC followed by slow warming to room temperature without removing of the cold bath. To the resulting bright orange solution was added ca. 2 g of silica gel, and the solvent was removed at water aspirator pressure on a rotary evaporator. The residue was transferred to the top of a column filled with silica gel and separated by flash chromatography. The product appeared as a bright orange band that was collected in a round-bottom flask. The solvent was removed with a rotary evaporator to give pure product. The products were stored in a freezer (-20 "C) until use, to minimize decomposition-oxidation. Most of these complexes began to decompose at room temperature within minutes of their preparation and acceptable elemental analyses could not be obtained. Pentacarbonyl[(methyI)(2-propen-I-oxy)carbene]chromium( 0)( 14a). From 1.00g (3.20 mmol) of 13,0.40 g (3.20 mmol) of acetyl bromide, and 0.18 g (3.20 mmol) of allyl alcohol with purification by flash chromatography [hexane/EtOAc (9:1)], 0.50 g (1.80 mmol, 56%) of 14a was obtained as an orange oil: 'H NMR (300 MHz, CDCI,, broad signals) 6 6.30 (s, 1 H), 5.40 (s, 4 H), 3.00 (s, 3 H, Me); 'IC NMR (75 MHz, CDCI,) 6 358.24 (Cr=C), 223.36 (trans-CO), 216.45 (4C, cis-CO), 132.67 (C2), 118.53 (C3), 80.13 (CI), 33.61 (Me); IR (film) Y 2064 (rruns-CO), 19 18 (br, cis-CO) cm-I. Pentacarbonyl[(3-buten-l-oxy)(methyl)carbene]chromium(O) (14b). From 2.00 g (6.40 mmol) of 13,0.79 g (6.40 mmol) of acetyl bromide, and 0.46 g (6.40 mmol) of 3-buten-1-01 after chromatography (hexane/ EtOAc, 9:l). 1.30 g (4.50 mmol,70%) of 14b was obtained as an orange oil: IH NMR (300 MHz, CDCI,) 6 5.88 (tdd, 1 H, J = 17.1, 10.3, 6.8 Hz, H-3), 5.20 (overlapping m, 2 H, H-4), 4.96 (br s, 2 H, H-I), 2.93 (s, 3 H, Me), 2.73 (tq, 2 H, J = 6.6, 1.2 Hz, H-2); "C NMR (75 MHz, CDCI,) 6 358.24 ( C d ) , 223.33 (trans-CO), 216.44 (4 C, cis-CO), 132.66 (C3), 118.48 (C4), 79.77 (CI), 49.18 (Me), 33.57 (C2); IR (film) Y 2060 (trans-CO), 1950 (br, cis-CO) an-'; MS (CI, NH,) 99 (M Cr(CO)5 + H'). Pentacarbonyl[(methyI)(>methyl-3buten-1 -oxy )carbenebhromium(O) (14~).From 3.09 g (10.00 mmol) of 13, 1.50 mL (12.00 mmol) of pivaloyl chloride, and 1.03 g ( I 2.00 mmol) of 3-methyl-3-buten-1-01after chromatography (petroleum ether), 1.39 g (4.60 mmol,46%) of 1 4was

4312 J . Am. Chem. SOC..Vol. 112, No. II. 1990 obtained as an orange oil: 'H NMR (270 MHz, CDCI,, broad signals) 6 4.90 (m,4 H, H-4, H-2), 2.94 (s, 3 H, Ct=CMe), 2.70 (s, 2 H, H-2), 1.84 (s, 3 H, Me-C3); I3C NMR (67.5 MHz, CDC13) 6 358.28 ( C d ) , 223.34 (trans-CO), 216.50 (4C, cis-CO), 140.49 (C3), 113.23 (C4), 78.98 (CI), 48.53 (Cr=CMe), 37.17 (Me-C3). 22.47 (C2); IR (film) Y 2050 (trans-CO), 1920 (br, cis-CO) cm-I; MS (CI, NH,) 113 (M Cr(CO)5 + H'). Pentacarbonyl[(trans -3-hexen-l-oxy)(methyl)carbene]chromium(O) (14d). From 3.09 g (10.00 mmol) of 13, 1.50 mL (12.00 mmol) of pivaloyl chloride, and 1.20 g (12.00 mmol) of trans-3-hexen-1-01 after flash chromatography (petroleum ether), 2.70 g (8.50 mmol,85%) of 14d was obtained as an orange oil: 'H NMR (300 MHz, CDCI,, broad signals) 8 5.69 (m, 1 H, C=CH), 5.48 (m, 1 H, C=CH), 4.91 (s, 2 H, H-I), 2.94 (s, 3 H, Cr=CMe), 2.68 (d, 2 H, J = 6.0 Hz), 2.07 (t, 2 H, J = 6.3 Hz), 1.01 (t, 3 H, J = 7.2 Hz, H-6); "C NMR (75 MHz, CDCIJ 8 357.58 (Cr=C), 223.45 (trans-CO), 216.48 (4 C, cis-CO), 136.44, 122.74, 80.87 (CI),49.07 (Me), 32.51, 25.59, 13.48 (C6); IR (film) Y 2040 (trans-CO), 191 5 (cis-CO) cm-I; MS (CI, NH,) 127 (M - Cr(CO)5 + H'). Pentacnrbonyl[(cis-3-hexen-1-oxy)( methyl)carbene]chromium(O) (Me). From 3.09 g (10.00 mmol) of 13, 1.50 mL (12.00 mmol) of pivaloyl chloride, and 1.20 g (12.00 mmol) of cis-3-hexen-1-01 after flash chromatography (petroleum ether), 2.47 g (7.80 mmol, 78%) of 14e was obtained as an orange oil: 'H NMR (300 MHz, CDCI,, broad signals) 6 5.47 (s, 2 H), 4.89 (s, 2 H), 2.91 (s, 4 H), 2.10 (s, 3 H), 1.00 (s, 3 H); "C NMR (75 MHz, CDCI,) 6 357.74 ( C d ) , 223.35 (trans-CO), 216.43 (4 C, cis-CO), 135.58, 122.38, 80.75 (CI), 49.28 (Cr=CMe), 27.29,20.62, 14.00 (C6); IR (film) Y 2045 (trans-CO), 1925 (br, cis-CO) an-'; MS (CI, N H J 144 (M - Cr(CO)5 + NH4'), 127 (M - Cr(CO)5

+ H').

Pentacarhony~(methyl)(4-penten-2-oxy)carbene]chromium(O)(14f). From 3.09 g (10.00 mol) of 13, 1.50 mL (12.00 mmol) of pivaloyl chloride, and 1.03 g (12.00 mmol)of 4-penten-2-01 after chromatography (petroleum ether), 1.99 g (6.60 mmol,66%) of 14f was obtained as an orange oil: 'H NMR (300 MHz, CDCI,, broad signals) 6 5.81 (m, 2 H, H-2, H-4), 5.18 (s, 2 H, H-5), 2.92 (s, 3 H, Cr=CMe), 2.61 (s, 2 H, H-3), 1.53 (s, 3 H, Me-C2); "C NMR (75 MHz, CDCI,) 6 353.30 (Cr=C), 223.35 (trans-CO), 216.47 (4 C, cis-CO), 131.89 (C4), 119.33 ((25). 89.24 (CZ), 50.04 (Cr=CMe), 40.71 (C3), 19.98 (CI); IR (film) Y 2062 (trans-CO), 1916 (cis-CO, br) cm-I; MS (CI, NH,) 113 (M Cr(CO), + H').

Pentacatbonyl[(methyI)(emethyl-3-penten-l-oxy)cnrbene]chromium(0) (14g). From 1.55 g (5.00 mmol) of 13, 0.39 mL (5.00 mmol) of acetyl bromide, and 0.46 g (4.60 mmol) of 4-methyl-3-penten-1-01 after chromatography (hexane), 0.94 g (3.00 mmol,64%) of 14g was obtained as an orange oil: 'H NMR (300 MHz, CDCl,, broad signals) 8 4.80 (s, I H, H-3). 4.48 (s, 2 H, H-I), 2.52 (s, 3 H, Cr=CMe), 2.28 (s, 2 H, H-2), 1.34 (s, 6 H, C=CMe2); "C NMR (75 MHz,CDCI,) 8 357.47 ( C d ) , 223.48 (trans-CO), 216.50 (4 C, cis-CO), 135.93 (C3), 118.00 (C4), 80.89 (CI), 49.68 (Cr=CMe), 28.27 (CZ), 25.68 (Me), 17.80 (Me); IR (film) Y 2025 (trans-CO), 1920 (br, cis-CO) cm-I; MS (CI, NHJ (M - Cr(CO)J H').

+

Pentacarbonyq(methyl)(epenten- I-oxy)carbene]chromium(O) (14h). From 3.09 g (10.00 mmol) of 13, 1.50 mL (12.00 mmol) of pivaloyl chloride, and I .03 g (12.00 mmol) of 4-penten-1-01 after chromatography (petroleum ether/Et20, 9:l), 2.08 g of an orange oil was obtained. The oil was dissolved in 50 m L of petroleum ether, washed with 2 X 75 mL of I M NaHCO, (aqueous) to remove pivalic acid, and dried with MgS04 to give, after solvent removal, 1.87 g (6.10 mmol,61%) of 14h as an orange oil: 'H NMR (300 MHz, CDCI,, broad signals) 6 5.83 (m, 1 H, H-4), 5.12-4.80 (overlapping m, 4 H, H-I, H-5), 2.94 (s, 3 H, Cr=CMe), 2.30 (m, 2 H, H-3), 2.10 (m,2 H, H-2); I3C NMR (75 MHz, CDCI,) 6 357.95 (Cr=C), 223.38 (rrans-CO), 216.47 (4 C, cisc o ) , 136.63 (C4), 116.07 (C5). 80.28 (CI), 49.13 (Cr=CMe), 29.87, 28.36; IR (film) Y (trans-CO), 1916 (br, cis-CO) cm-I; MS (CI, NH,) 113 (M - Cr(CO)5 + H'). Pentacarbonyl[[[ trams -2-(2-propenyl)cyclohexyl]oxy](methyl)carbene]chromium(O) (149. From 3.09 g (10.00 mmol) of 13,0.85 g (1 I .OO mmol) of acetyl bromide, and 1.68 g (12.00 mmol) of rrans-2-(2propenyl)-1-cyclohexanol after flash chromatography (hexane), 1.65 g (4.60 mmol, 46%) of 14i was obtained as an orange oil that slowly crystallized to yellow needles: mp 35-37 "C, 'H NMR (300 MHz, CDCI,, broad signals) 6 5.71 (s, 1 H, CH=CH2), 5.03 (s, 3 H, H-I, CH=CH2), 2.92 (s. 3 H, C d M e ) , 2.25-1.15 (m,1 1 H); "C NMR (75 MHz, CDCI,) 6 353.90 (Cr=C), 223.25 (trans-CO), 216.62 (4 C, cis-CO), 136.44 (CH=CH2), 116.26 (CH=CH2), 96.01 (CI), 50.24 (Cr=CMe), 42.32, 36.56, 32.73, 30.01, 24.66, 23.95; IR (film) Y 2060 (trans-CO), 1935 (br, cis-CO) cm-I. Anal. (Cl6HIBCrO,)C, H. Pentacarbonyl[(1,5-hexadien-3-oxy)(methyl)carbene]chromium(O) (14j). From 1.55 g (5.00 mmol) of 13. 0.75 mL (6.00 mmol) of pivaloyl

Soderberg et al. chloride, and 0.59 g (6.0 mmol) of 1,5-hexadien-3-01, after flash chromatography (petroleum ether), 0.87 g (2.80 mmol, 56%) of 14j was obtained as an orange oil: 'H NMR (300 MHz, CDCI,, broad signals) 6 6.0 (s, 1 H), 5.8 (s, 1 H), 5.2 (s, 5 H), 2.96 (s, 3 H, Cr=CMe), 2.70 (s, 2 H); I3C NMR (75 MHz, CDCI,) 6 355.97 (CFC), 223.51 (rrans-CO),216.36(4C,cis-C0), 134.43, 131.47, 119.61, 118.02,91.72 (C3), 49.80 (Cr==CMe), 39.60 (C4); IR (film) Y 2062 (trans-CO), 1921 (br, cis-CO) cm-I; MS (CI, NH,) 125 (M - Cr(CO), + H'). Pentacarhonyl((3-hexyn-1-oxy)methyl)carbene]chromium(O) (14k). From 1.55 g (5.00 mmol) of 13,0.75 mL (6.00 mmol) of pivaloyl chloride, and 0.59 g (6.00 mmol) of 3-hexyn-1-01after flash chromatography (petroleum ether/Et20, 9:l), 1.51 g of an orange oil was obtained. The oil was rechromatographed, to remove pivalic acid, eluting with petroleum ether to give 0.82 g (2.60 mmol,52%) of 14h as an orange oil: 'H NMR (200 MHz, CDCI,) 6 4.95 (br s, 2 H, H-I), 2.97 (s, 3 H, Cr= CMe), 2.85 (tt, 2 H, 52.1 = 6.5, J2.5 = 2.3 Hz, H-2), 2.16 (tq, 2 H, J5.6 = 7.5, 55.2 = 2.4 Hz, H-5), 1.10 (t, 3 H, J6.5 = 7.6 Hz, H-6); "C NMR (75 MHz, CDCIJ) 6 358.76 (CFC), 223.35 (trans-CO), 216.29 (4 C, cis-CO), 84.56, 78.56 (CI), 73.61, 48.97 (Cr=CMe), 20.04, 13.88, 12.29; 1R (film) Y 2050 (trans-CO), 1920 (br, cis-CO) cm-l; MS (CI, NH,) 125 (M - Cr(CO)5 H'). Pentacnrhonyl((methyl)(4-pentyn-l-oxy)carbene]chromium(O) (141). From 3.09 g (10.00 mmol) of 13, 1.50 mL (12.00 mmol) of pivaloyl chloride, and 1.01 g (12.00 mmol) of 4-pentyn-1-01 after flash chromatography (petroleum ether/Et20, 9:l), 2.26 g of an orange oil was obtained. The oil was rechromatographed to remove pivalic acid (petroleum ether) yielding 1.91 g (6.30 mmol, 63%) of 141 as an orange oil: 'H NMR (300 MHz, CDC13), 6 4.99 (br s, 2 H, H-I), 2.95 (s, 3 H, Cr= CMe), 2.46 (dt, 2 H, 53.2 = 6.7, J3,5 = 2.3 Hz, H-3), 2.20 (quin, 2 H, J2.1 = J2.3 = 6.4 Hz, H-2), 2.02 (t, 1 H, J5.4 = 2.5 Hz, H-5); "C NMR (75 MHz, CDC13) 6 358.72 (Cr=C), 223.37 (rrans-CO), 216.35 (4 C, cis-CO), 81.99 (C4), 79.06 (CI), 69.86 (C5), 49.29 ( C r l M e ) , 27.95, 26.88; IR (film) Y 331 1 ( C e - H ) , 2063 (trans-CO), 1942 (br, cis-CO) an-'. Pentacarbonyl[(methyl)( 10-undecen-1-oxy)carbene]chromium( 0) (14m). From 3.09 g (10.00 mmol) of 13, 1.50 mL (12.00 mmol) of pivaloyl chloride, and 2.04 g (1 2.00 mmol) of IO-undecen- 1-01 after chromatography (petroleum ether), 2.86 g (7.40 mmol,74%) of 14m was obtained as an orange oil: 'H NMR (300 MHz, CDCI,, broad signals) 6 5.80 (s, 1 H, H-IO), 4.94 (s, 4 H, H-I, H-l I), 2.92 (s, 3 H, C d M e ) , 2.00 (s, 4 H), 1.32 (s, 12 H); 13C NMR (75 MHz, CDCI,) 6 357.33 ( C d ) , 223.36 (trans-CO), 216.49 (4 C,.cis-CO), 139.04 (CIO), 114.08 (CII), 81.70 (CI), 49.51 (Cr=CMe), 33.74, 29.27 (6C), 25.78; IR (film) Y 2062 (trans-CO), 1922 (cis-CO) cm-I. Pentacarhonyl((3-cyclohexen-1ylmethy1)oxy) (methyl)carbene]chromium(0) (14n). From 1.55 g (5.00 mmol) of 13.0.43 mL (5.50 mmol) of acetyl bromide, and 0.67 g (6.00 mmol)of 3-cyclohexene-I-methanol after flash chromatography (hexane), 0.44 g (1.30 mmol, 26%) of 14n was obtained as an orange oil: 'H NMR (300 MHz, CDCI,, broad signals) 8 5.72 (s, 2 H, CH=CH), 4.78 (s, 2 H, OCH,), 2.95 (s, 3 H, Cr==CMe), 2.29 (s, 2 H), 2.14 (s, 2 H), 1.93 (s, 2 H), 1.52 (s, 1 H); "C NMR (75 MHz, CDCIJ 8 357.80 ( C M ) , 223.41 (trans-CO), 216.52 (4 C, cis-CO), 127.15, 125.04, 85.54 (CI), 49.61 ( C d M e ) , 33.84, 27.90, 25.11, 24.24; IR (film)Y 2062 (trans-CO), 1921 (br, cis-CO) an-'. General Procedure for the Preparationof Bicyclic Cyclobutanones 15. In an oven-dried Fischer Porter pressure vessel was placed a -0.1 M yellow solution of the carbene in diethyl ether or acetonitrile. The vessel was saturated with CO-three cycles to 90-100 psi of CO-and irradiated (450-W Hanovia lamp) for -24 h under 90 psi of CO. The now colorless solution was removed with a pipet to leave crystalline Cr(C0)6 and some green precipitate. The solvent was removed on a rotary evaporator at water aspirator pressure to give a white semisolid composed of product and Cr(CO)6. The crude material was triturated with a few milliliters of petroleum ether, the solution was put on top of a column and flash chromatographed by elution with first petroleum ether and then a mixture of petroleum ether/Et,O, to give, after solvent removal on a rotary evaporator, the pure cyclobutanone. l-Methyl-2-oxnbicyc~3.2.O~ptan-7-ow (15b). From irradiation of 1.20 g (4.13 mmol) of 14b in 30 mL of E t 2 0 at 90 psi of C O for 23.5 h after chromatography (petroleum ether/EtiO, 1:1,50 mL), 0.46 g (3.65 mmol,88%) of 15b was obtained as a colorless oil: 'H NMR (270 MHz, CDCI3) 6 4.19 (t, 1 H, JJ33,= 53.4 = 8.7 Hz, H-3), 3.76 (ddd, 1 H, Jy.4 = 11.7, J3,q3= 9.4, J3,.4, = 5.5 HZ, H-30, 3.1 1 (dd, 1 H, J6.6, = 18.6, J6.5 = 9.6 HZ, H-6), 2.67 (dt, I H, J5,4 J5.6 = 8.8, J5,6t = 4.9 HZ, H-5), 2.44 (dd, I H, J6,,6 = 18.6, J6r.j = 4.9 HZ, H-69, 2.10 (tt, I H, J ~ , J J4.4, = 12.2, J4.3 = J4.5 = 7.9 Hz, H-4), 1.87 (dd, 1 H, J4t.4 = 12.7, J4,,3, = 5.4 Hz, H-4'), 1.37 (s, 3 H, Me); I3C NMR (70 MHz, CDCI,) 6 213.44 (CO), 100.41 (Cl), 68.93 (C3), 47.51 (C6), 36.38 (CS), 32.44 (C4), 15.97 (Me); IR (film) Y 1775 (CO) cm-I; MS (CI, NH,) 144 (M +

+

Reaction of Chromium Carbene Complexes with Olefins

+

NH4'), 127 (M H'); MS (El) 98 (M'Anal. (C7HI0O2)C, H.

CO), 84 (M'

-C

H 4 4 ) .

J . Am. Chem. Soc.. Vol. 112, No. 11. 1990 4313 (m, 1 H, H-59, 1.35 (s, 3 H, Me); 13C NMR (75 MHz, CDCI,) 6 209.05 (CO), 88.35 (CI), 64.33 (C3), 47.43 (C6), 29.79, 26.14, 21.57 (Me), 21.48; IR (film) v 1780 (CO) cm-I; high-resolution mass spectrum calcd for C8Hl2O2140.0837, found 140,0841. Cyclobutanone (1Sh) and l-Methyl-2.9-dioxabicyclo(4.3.0~-8-o. A solution of 0.30 g (1.00 mmol)of 14h in MeCN was irradiated for 15 h as described in the general procedure but in the absence of CO. The solvent was removed on a rotary evaporator at water aspirator pressure to give a yellow solid. The solid was dissolved in EtOAc and filtered through Celite, and the solution was diluted with one volume of hexane. The mixture was air oxidized in a light box (6 X 20 W Vitalite fluorescent bulbs) for 40 h. The brown precipitate was removed by filtration, and the solvent was removed on a rotary evaporator to give 0. I5 g of a pale yellow oil. Flash chromatography eluting with hexane/EtOAc (8:2) gave first 0.06 g (0.43 mmol,43%) of 15h followed by 0.3 g (0.19 mmol, 19%) of 1-methyl-2,9-dioxabicyclo[4.3.0]nonan-8-one both as colorless oils. The latter has the following spectral data: ' H NMR (300 MHz, CDCI,) 8 3.74 (m,2 H, H-3), 2.69 (dd, 1 H, J7,71= 17.2, J7.6 = 7.4 Hz, H-7), 2.38 (dd, 1 H, J7,,7 = 17.2, J78.1 = 4.2 Hz, H-7'), 2.28 (m,1 H), 1.91 (m,I H), 1.59 (m,3 H), 1.53 (s, 3 H, Me); 13C NMR (75 MHz, CDCI,) 8 174.42 (CO), 107.51 (CI), 62.73 (C3), 37.36 (C6), 36.39 (C7), 24.92, 24.48 (Me), 21.28; IR (film) v 1771 (CO) cm-I; high-resolution mass spectrum calcd for C8HI2O3156.0786, found 156.0793. Tricyclic Ketones 15i and 15i'. A 359-mg portion (1 .OO mmol) of 14i was irradiated for 23.5 h at 90 psi of C O as described in the general procedure. The solvent was removed on a rotary evaporator to give a white semisolid that was triturated with a few milliliters of EtOH (100%) and filtered through a 0.5-cm-thick Celite pad. Removal of solvent on a rotary evaporator gave 189 mg (0.97 mmol, 97%) of a 2:l mixture 15i and 15' as an almost colorless oil. Data from a ca. 65:35 mixture: ' H NMR (300 MHz, CDCI,) 6 3.27 (dd, 1 H, J = 16.7, 10.0 Hz), 3.03 (m, 2H),2.95(dd,I H , J = 16.1,7.9Hz),2.85(dd,I H , J = l 6 . 7 , 9 . 3 H z ) ,

1,5-Dimethyl-2-owbieyclo(3.2.0~~-7-o ( 15c). From irradiation of 841 mg (2.77 mmol) of 14c in 25 mL of Et,O at 90 psi of C O for 30 h after flash chromatography (petroleum ether/Et20, 8:2), 240 mg (1.71 mmol, 62%) of 15c was obtained as a colorless oil. Spectral data was in complete accordance with literature values.20 exo-CEthyl-l-methyl-2-oxabicyclo[3.2.0]heptan-7-one (1%). Irradiation of 1.27 g (4.00 mmol) of 1 4 for 19 h, after flash chromatography (petroleum ether/Et20, 9:l), gave 0.29 g (1.89 mmol, 47%) of 15d as a colorless oil: 'H NMR (300 MHz, CDCI,) 8 4.22 (t, 1 H, J,,,, = J3,4= 8.6 Hz, H-3), 3.78 (ddd, I H, J3,,4 = 11.7, J3,,3 = 9.7, JJt,4t = 5.4 Hz, H-3'), 2.56 (ddd, 1 H, J 6 . c ~ ~ '7.0, J6.5 = 5.2 Hz, H-6), 2.37 (dd, 1 H, Jj.4 = 7.5, Jj.6 5.2 Hz, H-5), 2.1 1 (tt, 1 H, J4.3, = J4.4, = 12.1, J4.3 = J4,5 = 7.8 Hz, H-4), 1.91 (dd, 1 H, J4r.4 = 12.5, Jd,,,, 5.4 Hz, H-49, 1.71 (apparent octet, 1 H, J = 7.2 Hz, CH2CH,), 1.59 (m, 1 H, CH,CH3), I .37 (s, 3 H, MeCI), 0.97 (t, 3 H, J = 7.4 Hz, CH2CH3);I3C NMR (75 MHz, CDCII) 6 215.47 (CO), 98.01 (CI), 69.23 (C3), 62.98 (C6), 43.26 ((29, 32.69 (C4), 23.06 (CH,), 16.81 (Me-'25). 11.87 (CH,CH,); IR (film) Y 1775 (CO) cm-I; MS (CI, NH,) 172 (M + NH4'), IS5 (M + H'). Anal. (C9HI4O2)C, H. endo -7-Ethyl-1-methyl-2-0xabicyclo(3.1.1 bptan-6-one (1 W) and endo-6-Ethyl-l-methyl-2-owbi~yclo[3.20~~7-one (1%). From 1.27 g (4.00 mmol) of 14e after irradiation for 22.5 h and flash chromatography (petroleum ether/Et20, 9:l), 137 mg (0.64 mmol, 22%) of 1%' followed by 181 mg (0.84 mmol,29%) of 15e was obtained as colorless oils. Cyclobutanone 15e': 'H NMR (300 MHz, CDCI,) 6 3.99 (dd, 1 H, J3.49 = 1 I .5, J3.4 = 7.5 Hz, H-3). 3.82 (dt, 1 H, J3:3 = J3,,4 11.7, J3,.4, = 5.8 Hz, H-39, 3.22 (t, I H, J5.4 = 55.7 = 5.7 Hz, H-5). 2.50 (dt, 1 H, J4,3, = 54.4' 5 12.4, J4.3 = 7.6 Hz, H-4), 1.96 (td, I H, J4t.4 = 12.5, J4,,,, = J4,,5 = 6.2 Hz, H-4'). 1.83-1.64 (m,3 H, H-7, CHI), 1.21 (s, 3 H, Me-CI), 0.99 (t, 3 H, J = 6.9 Hz, Me); I3C NMR (75 MHz, CDCI,) 6 207.36 (CO), 95.15 (CI), 63.67 (C3), 57.89 (C5), 41.76 (C7), 26.77 2.24(m,3H),2.11(dd,1H,J=15.9,1.8Hz),1.9-1.4(m,11H),1.38 (C4), 16.74, 15.37, 12.38; IR (film) Y 1776 (CO) cm-I; MS (CI, NH,) (s, 3 H, Me), 1.28-0.77 (m, 10 H), superimposed on 1.23 (s, 3 H, Me); 172 (M + NH4'), 155 (M + H'). Anal. (C9HI4O2)C, H. I3C NMR (67.5 MHz, CDC13) 8 209.79 (CO), 204.22 (CO), 89.39, Cyclobutanone 1Se: 'H NMR (300 MHz, CDCI,) 8 4.10 (t. 1 H, J,,,. 88.58, 77.71, 75.75, 47.96, 46.94, 37.25, 35.79, 35.12, 32.58, 32.47, 31.78, J3.4 = 8.7 Hz, H-3), 3.55 (ddd, I H, J3f.4 = 11.4, J3f.3 9.5, JJr.4, 31.68, 31.33, 30.24, 29.72, 25.55, 25.46, 24.91, 24.56, 23.28, 16.54; IR 6.0 HZ, H-37, 3.04 (ddd, I H, J6.5 = 10.4, J6,cH1 = 8.6, J 6 . c ~ ~ '7.2 Hz, (film) Y 1785 (CO) cm-I; MS (El): 194 (M'). Anal. (CI2Hl8O2)C, H-6), 2.71 (t, 1 H, Js,6 = J s , 4 = 9.7 Hz, H-5), 1.99 (m,1 H, H-4), 1.87 H. Found: C, 74.37; H, 9.17. (dd, 1 H, J4,,4= 13.2, J4,,3, = 5.9 Hz, H-47, 1.62 (septet, 1 H, J = 7.3 5-Methyl-l-phenyl-2-oxabicyclo(3.I.OJhexane(17). Carbon monoxide Hz, CH,), 1.42 (s, 3 H, MeCI), 1.32 (septet, 1 H, J = 7.4 Hz, CH,'), was bubbled through a solution of 714 mg (1.92 mmol) of penta0.95 (t, 3 H, J 7.4 Hz, CHzCH3); 13C NMR (75 MHz, CDCl3) 8 carbonyl[ [(tetramethylammonio)oxy](phenyl)carbene]chromium(0) in 217.27 (CO), 98.32 (CI), 69.66 (C3), 56.84 (C6), 39.92 (CS), 26.47, 25 mL of CH,CI2 for 15 min, the solution was cooled to -40 OC put 16.32 (2 C), 12.32; IR (film) v 1782 (CO) cm-I; MS (CI, NH,) 172 (M under C O atmosphere, and 295 p L (2.40 mmol) of pivaloyl chloride was + NH4+), 155 (M + H'). Anal. (CgH&) C, H. added by syringe. After 1 h at -35 i 5 "C, 206 mg (2.40 mmol) of 1,3-Dimethyl-2-oxabicyci~3.2.O]heptan-7-one (150. From 9 12 mg 3-methyl-3-buten-l-ol in 6 mL of CH2CI2was added by syringe and the (3.00 mmol) of 14f after irradiation for 20 h and flash chromatography vessel was pressurized to 90 psi of CO. The reaction mixture was allowed (petroleum ether/Et,O, 9:l), 242 mg (1.86 mmol,62'16, endo/exo, I 1 : l ) to warm to room temperature overnight ( 1 5 h) and was then irradiated of 15f was obtained as a colorless oil. endo-151 (from an 11:l mixture): under 90 psi of C O for 24 h. Evaporation of the solvent, on a rotary 'H NMR (300 MHz, CDCI3) 8 4.45 (sextet, 1 H, J3,4= J3,4t= J3,Me = evaporator, from the yellow solution gave a yellow solid-oil. The pre6.5 Hz, H-3), 3.17 (m, 1 H, H-6), 2.82-2.69 (m,2 H, H-5, H-69, 2.51 cipitate was triturated with petroleum ether and filtered through Celite (ddd, I H, 54.41 = 13.1, 54.5 = 9.0, J4.3 = 6.5 Hz, H-4), 1.61 (ddd, 1 H, to give, after solvent removal, 607 mg of a pale green oil with some solid J4,,4= I ~ . I , J ~ , , J = ~ . ~ , J ~ , , ~ = ~ . S 1H. 3 Z8,(H~ ,-3~H' ,)M, e C l ) , l . 2 8 Cr(CO)6. The oil was purified by radial chromatography (2-mm plate, ~ Hz, ~ M e C 3 ) ; "C NMR (75 MHz, CDCI3) d 210.58 (d, 3 H, J M =~ 6.4 petroleum ether/Et20, 9 5 5 ) to give, after solvent removal, 407 mg of (CO), 100.64 (CI), 80.15 (C3). 48.62 (C6), 41.37 (C5), 37.31 (C4), a colorless oil. The oil was rechromatographed on a 16 X 2.5 cm column 21.55 (Me), 16.41 (Me); IR (film) Y 1783 (CO) cm-I; MS (CI, NH,) eluting with first petroleum ether (40 mL) followed by petroleum eth158 (M + NH4'), 141 ( M + H+). Anal. (C8H1402)C. H. er/Et20 (9: I ) to give, after solvent removal, 279 mg (1.60 mmol, 83%) exo-15; (partial spectra from an 11:l mixture): 'H NMR (300 MHz, of 17 as a colorless oil: 'H NMR (300 MHz, CDCI,) 6 7.3 (m,5 H, = 5.7 Hz, H-3), 2.01 CDCI,) 8 4.13 (sept, 1 H, J3.4= 11.4, J3,4t= J3,Mc ArH), 4.16 (dt, 1 H, J,,,, = J3,4= 8.7, J3,4t= 3.1 Hz, H-3), 3.60 (td, 1 (dd, 1 H, J4,4,= 12.7, J4,, = 4.7 Hz, H-4), 1.74 (m,1 H, H-40, 1.40 (s, H, J3,,4,= J,.,, = 9.6, J3,,4= 7.8 Hz, H-39, 2.09 (m,2 H, H-4), 1.34 (d, 3 H, Me-CI), 1.33 (d, 3 H, J M ~ ,= , 5.9 Hz, Me-C3); I3C NMR (75 1 H, J66' = 6.6 Hz, H-6), 1.01 (s, 3 H, Me), overlapping 1.00 (d, 1 H, MHz, CDCI3) 8 214.01 (CO), 99.92 (CI), 75.77 (C3), 48.41 (C6), 39.89 H-6'); I3C NMR (75 MHz, CDCI,) 6 137.51 (ipso)* 127.86, 127.12, (CS), 37.05 (C4), 19.54 (Me), 16.01 (Me). 126.84, 72.58 (CI), 65.49 (C3), 35.75 (C4), 29.06 (CS), 17.90, 17.64; 1,7,7-Trimethyl-2-oxabicyclo(3.l.l~ptan-6-one(1%). Irradiation of IR (film) v 3063,3029,2944,2868, 1449, 1128, 1070, 1041, 1027,765, 0.32 g (1.00 mmol)of 14g, after chromatography (petroleum ether/Et,O, 698 cm-I; MS (CI, NH3) 192 ( M + NH,'), 175 (M + H'). Anal. 9:l), gave 0.12 g (0.80 mmol,80%) of 15g as white crystals: ' H NMR (C12H140) c , H. (270 MHz, CDCI,) 6 4.00 (dd, 1 H, J3,3, = 11.5, J3,4 7.7 Hz, H-3), Pentacarbonyl[(cyclopropyl)(3-methyl-3-buten-1-oxy)carbene]chro3.82 (dt, 1 H, J3t3 = J3r.4 = 11.6. J y , y = 6.0 Hz, H-3'), 2.80 (d, 1 H, Jj.4, mium(0) (18). Similar treatment of 1.68 g (5.00 mmol) of penta= 5.7 Hz, H-5), 2.59 (dt, I H, J4.49 = J4.3, = 12.6, J4.3 7.8 Hz, H-4), carbonyl [(cyclopropyl) [tetramethylammonio)oxy]carbene]chromium(0) 2.06(td,I H , J 4 ~ 4 = 1 2 . 5 , J 4 ~ , , = J 4 ~ , I = 6 . 1 H ~ . H - 4 ' ) , 1 . 2 1 ( s , 3 H , M e )with , first 0.75 mL (6.00 mmol) of pivaloyl chloride in 150 mL of CH,C12 1.05 (s, 3 H, Me), 1.00 (s, 3 H, Me); I3C NMR (75 MHz, CDCI,) 6 for 80 min at -35 "C and then 0.52 g (6.00 mmol) of 3-methyl-3-bu209.58 (CO), 95.30 (CI), 63.89 (C3), 62.63 (C5), 35.55 (C7), 29.60 ten- 1-01 in 6 mL of CHzC12 for 2 h followed by slow warming to room (C4), 29.1 3, 14.08, 11.90; IR (film) Y 1780 (CO) em-'; MS (CI, NH3) temperature (17 h) as described in the general procedure gave, after flash 155 ( M + H'). Anal. (C9HI4O2)C, H. chromatography (13 X 2.5 cm column, petroleum ether), 1.16 g (3.52 l-Methyl-2-oxabicyclo(4.2.O~tan-8-one (15h). Irradiation of 1.22 g mmol,70%) of 18 as an orange oil that crystallized when stored in freezer (4.00 mmol) of 14h for 24 h, after chromatography (petroleum ether/ (-18 "C): mp e 2 0 "C; 'H NMR (300 MHz, CDC13, broad signals) 8 Et20, 9 : l ) gave 0.41 g (2.93 mmol, 73%) of 15h as a colorless oil: 'H 5.01 (s, 2 H, H-1). 4.91 ( s , 1 H, H-4), 4.82 (s, 1 H, H-4'). 3.46 (s, 1 H, NMR (300 MHz, CDCI,) 6 3.74 (m,1 H, H-3), 3.58 (m,1 H, H-3'), cyclopropyl-CH), 2.62 (s, 2 H, H-2), 1.82 (s, 3 H, Me-C3), 1.39 (s, 2 2.95 (dd, 1 H, J7.7, 16.5, J7.6 8.8 Hz, H-7), 2.43 (dd, 1 H, J7t.7 = 16.6, H, cyclopropyl-CH,), 1.18 (s, 2 H, cyclopropyl-CH,); I3C NMR (300 57.6 = 3.9 Hz, H-7'1, 2.21 (m, 2 H, H-5, H-6), 1.50 (m,2 H, H-4). 1.37 MHz, CDCI,) d 351.34 (CFC), 223.55 (trans-CO), 216.81 (4 C, cis-

4374

J. Am. Chem. SOC.1990, 112, 4374-4380

CO), 140.65 (C4), 113.14 (C3), 78.06 (CI), 41.54, 37.25, 22.11, 17.91 (2 C); 1R (film) Y 2060 (trans-CO), 1917 (br, cis-CO); MS (CI, NH,) 139 (M - Cr(CO)5 + H').

Pentacerbonyq(benzyl)( 3-methyl-3-buten-l-oxy)carbemelchromiurn(O) (19). Reaction of 1.93 g (5.00 mmol) of pentacarbonyl[(benzyI)[(tetramethylammonio)oxy]carbene]chromium(O) with first 0.45 mL (6.00 mmol) of acetyl bromide in 75 mL of CH2C12for 1 h at -35 OC and 0.52 g (6.00 mmol) of 3-methyl-3-buten-1-01in 6 mL of CH2CI2as described in the general procedure. After standard isolation by flash chromatography (petroleum ether) an orange oil (1.01 g) was obtained. The oil was rechromatographed (petroleum ether/Et20, 95:5) to give 0.38 g (1 .OO mmol, 20%) of 19 as orange crystals: mp 43-45 "C; 'H NMR (300 MHz, CDCI,, broad peaks) 6 7.28 (s, 3 H, Ar), 7.14 (s, 2 H, Ar), 5.09 (s, 2 H, ArCH,), 4.86 (s, 1 H, H-4), 4.72 (s, 1 H, H-4'). 4.59 (s, 2 H, H-I), 2.61 (s, 2 H, H-2), 1.74 (s, 3 H, Me-C3); "C NMR (75 MHz, CDCI,) 6 355.93 (Cr=C), 223.00 (trans-CO), 216.25 (4 C, cis-CO), 140.23, 134.84, 129.61, 128.45, 126.87, 113.32 (C4), 80.11 (CI), 68.27 (ArCH,), 36.96 (C2). 22.26 (Me-C3); IR (film) Y 2062 (trans-CO), 1924 (br, cis-CO); MS (CI, NH,) 206 (M - Cr(CO), + NH,'), 189 (M Cr(CO)5 + H'). l-Cyclopropyl-5-methyl-2-oxabicycl~3.2.O]heptan-7-one (20). Irradiation of 660 mg (2.00 mmol) of 18 for 22 h, after chromatography (petroleum ether/Et20, l : l ) , gave 214 mg (1.29 mmol, 65%) of 20 as a colorless oil: 'H NMR (300 MHz, CDCI,) 6 4.01 (ddd, 1 H, J,,,, = 9.4, J3,4, 8.1, J3.4 = 1.2 Hz, H-3), 3.57 (ddd, 1 H, J3t.4, = 11.7, J 3 r . 3 = 9.5, J3:4 = 5.5 HZ,H-37, 2.67 (dd, 1 H, J6.6' = 18.4, J = 0.8 HZ, H-6), 2.54 (d, 1 H, J6t.6 = 18.5 Hz, H-6'), 1.95 (ddd, 1 H, Jd.4, 1 1 . 6 , J 4 , ~= = J4t.3, = 1 1.7, J4f.3 = 8.1 Hz, 5.5, J4.3 = 0.9 Hz, H-4), 1.77 (dt, 1 H, H-4'). 1.36 (s, 3 H, Me), 0.78 (tt, 1 H, JI = 8.2, J2 = 5.3 Hz, cyclc-

propyl-CH), 0.43 (m. 3 H, cyclopropyl-CH2),0.22 (m,1 H, cyclopropyl-CH2); I3C NMR (75 MHz, CDCI,) 6 21 1.80 (CO), 108.10 (CI), 67.33 (C8), 54.89 (C6). 41.58 (C5), 39.98 (C4), 21.13 (Me), 7.89 (cyclopropyl), 0.55 (cyclopropyl), -0.29 (cyclopropyl); IR (film) Y 1776 cm-I; MS (CI, NH,) 167 (M + H'). Anal. (CIOHI4O2) C, H. 1-Benzyl-5-methyl-2-oxabicycl~3.2.O]heptan-7-one (21). Irradiation of 380 mg ( 1 .OO mmol) of 19 for 4 h gave, after chromatography (petroleum ether/Et20, 3:l), 205 mg (0.95 mmol, 95%) of 21 was white crystals: mp 51-52 OC; ' H NMR (300 MHz, CDCI,) 6 7.24 (m, 5 H, Ar), 4.14 (ddd, 1 H, J,,,, = 9.3, J3,4t = 8.3, J3,4 = 0.9 Hz, H-3), 3.71 (ddd, I H, J3r.4, = 11.7, = 9.6, J3*,4= 5.6 Hz, H-3'), 3.06 (d, 1 H, JSem= 14.8 Hz, ArCH,), 2.84 (d, 1 H, JBsm= 14.9 Hz, ArCH,), 2.78 (d, 1 H, J6,6, = 18.7 HZ, H-6). 2.69 (d, 1 H, J6f.6 = 18.4 HZ, H-6'). 1.99 (dd, I H, J4,4# = 12.4, J4.3, = 5.4 Hz, H-4), 1.76 (dt, 1 H, J4f.4 = J4,,3, = 12.1, J4,,,= 8.2 Hz, H-49, 1.34 (s, 3 H, Me); I3C NMR (75 MHz, CDCI,) 6 211.48 (CO), 135.53 (ipso), 130.03, 127.83, 126.27 (para), 100.07 (CI), 67.46 (C3), 54.69 (ArCH,), 42.06 (C5), 39.72 (C6), 34.29 (C4), 21.09 (Me); IR (film) Y 1776 (CO) cm-I; MS (CI, NH,) 234 (M + NH,'), 217 (M H'). Anal. (C1,HL6O2):C, H.

+

Acknowledgment. Support for this research under Grant 2 R01 GM26178-10 from the National Institutes of General Medical Sciences (Public Health Service) is gratefully acknowledged. M.A.S. thanks the Ministerio de Educacion y Cienca Espana for a postdoctoral fellowship. Mass spectrometry determinations were performed by Midwest Center for Mass Spectrometry, a National Science Foundation Regional Instrumentation facility (Grant No. CHE-8620177).

A Concise Approach to Enantiomerically Pure Carbocyclic Ribose Analogues. Synthesis of (4S,5R,6R,7R)-7 4Hydroxymethy1)spiro[ 2.41heptane-4,5,6-triol 7-0-( Dihydrogen phosphate) John J. Gaudino and Craig S. Wilcox* Contribution from the Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15260. Received October 2, I989

Abstract: This paper describes a synthesis of 5, an analogue of 5-phospho-a-D-ribofuranoseand instantiates a unique new approach to optically active carbocyclic analogues of ribofuranosides. The synthesis of 5 follows a general scheme that is outlined in brief retrosynthetic fashion in eq 1. The polyhydroxylated spiro[2.4]heptane (5) may be prepared via a suitably protected polyhydroxylated methylene cyclopentane A. The novelty of the synthetic approach described here is illustrated in the excision of the exocyclic methylene unit from the cyclopentanoid nucleus to generate a linear pentanose fragment (B)and a vinylidene fragment (C). In the forward direction, two carbon-carbon bonds are to be formed to the same carbon atom of this excised vinylidene fragment (C) and in this way two remote carbons on the pentanose skeleton B are "united" to form the methylenecyclopentane ring. The carbocyclic D-ribofuranose analogue 5 is prepared in seven steps and 7% overall yield from a D-ribofuranose starting material. The method is recommended to be generally serviceable for preparing carbocylic furanoside analogues.

The "carba" analogues of carbohydrates include carbocylic analogues, wherein the oxygen atom contained within the usual furanoid or pyranoid rings has been replaced with a carbon atom, and C-glycosides, wherein the anomeric oxygen atom has been replaced with a carbon atom.' While carbocyclic carbohydrate analogues, for example, aristeromycin (I)* and neplanocin (2),3 ( I ) Slotin, L. A. Synthesis 1977,737. (2) Kusaka, T.; Yamamoto, H.; Shibata, M.; Muroi, M.; Kishi, T.; Mizuno, K. J. Anribiot. 1968,21, 255. (3) Yaginuma, S.;Muto, N.; Tsujino, M.; Sudate, Y.; Hayashi, M.; Otani, M.J. Antibiot. 1981,34, 359-366.

have been isolated from natural sources, the great majority of such analogues have been produced through laboratory syntheses. The synthesis of carbocyclic ribonucleoside analogues has been motivated by an urgent need for antiviral agents and continues to be an especially active subdiscipline within this general area.* Carbocyclic ribose and deoxyribose analogues have been prepared by several methods in racemic form and, more rarely, in optically pure form. An important early example was the prep(4) Antiviral Agents: The Development and Assessment of Antiviral Chemotherapy; Field, H. J.. Ed.;CRC Press: Boca Raton, FL, 1988.

0002-7863/90/ 15 12-4374$02.50/0 0 1990 American Chemical Society